July 2026¶

July 9, 2026
in Paper Spotlight
2 min read

cGAS inhibitor IMSB301 modifies interferon signalling in peripheral mononuclear cells of SAMHD1 genetic interferonopathy in vitro

The finding

Using single-cell RNA sequencing, the authors profiled PBMCs from a single patient with biallelic (fully loss-of-function) SAMHD1-related Aicardi-Goutières syndrome and an age/sex-matched control. At baseline, the patient's cells showed strong upregulation of antiviral and type I interferon response pathways, led by classic ISGs (IFIT1, IFIT3, IFI44L, ISG15, OAS1). Treating patient PBMCs in vitro for 24 hours with IMSB301, a clinical-stage cGAS inhibitor, brought expression of these same top ISGs — and the enriched pathways they define — back down toward control levels.

Where it fits

This is squarely ARM 1 (interferon/JAK-STAT) evidence: it targets cGAS, the upstream DNA-sensing node that feeds STING → IRF3/7 → tonic type I IFN. For the SAMHD1 A565T model, it supports the idea that cGAS-STING sensing is a druggable point of entry upstream of the ANKIB1 gain-control node, and it's a proof-of-concept that pharmacologically dialing back cGAS activity can normalize an ISG signature driven by SAMHD1 dysfunction. Because ARM 1 is described as JAK-inhibitor-responsive, this cGAS-targeted approach offers a complementary, potentially more upstream lever on the same arm — relevant to thinking about combination or alternative strategies if JAK inhibition alone is insufficient or if ARM 2/3 activity persists.

Caveats

This is biallelic, fully loss-of-function SAMHD1 (classic AGS), not the heterozygous, partial loss-of-function A565T variant central to this project — the degree of cGAS/STING pathway engagement may differ substantially.
N = 1 patient, PBMCs only, in vitro drug exposure — no data on primary cell types most relevant to A565T biology (e.g., monocytes/macrophages, endothelium) and no in vivo or clinical outcome data.
The study shows transcriptional correlation (ISG downregulation) with cGAS inhibition, not direct mechanistic proof that cGAS-STING signaling is the dominant driver of baseline ISG elevation versus other sensors (e.g., MDA5) or arms (mitochondrial, NLRP3).

What to watch

The key open question is whether IMSB301 or similar cGAS inhibitors produce comparable ISG suppression in heterozygous, partial-function SAMHD1 A565T cells, and whether such suppression extends to ARM 2/3 readouts (mtDNA release, NLRP3 activation) or remains confined to ARM 1.

Source: cGAS inhibitor IMSB301 modifies interferon signalling in peripheral mononuclear cells of SAMHD1 genetic interferonopathy in vitro — 2026.

July 9, 2026
in Paper Spotlight
2 min read

One mutation, divergent journeys: expanding the clinical spectrum of homozygous SAMHD1 deficiency in childhood

The finding

This retrospective case series describes three pediatric patients who all carry the same homozygous SAMHD1 missense variant (p.Gly209Ser) yet present with strikingly different clinical pictures — ranging from a myopathy-dominant phenotype with no CNS involvement, to classic Aicardi-Goutières-like disease with intracranial calcifications and panniculitis, to a lupus-like connective tissue disease with calcinosis and vasculopathy. All three received JAK inhibitors (mostly tofacitinib) and showed partial-to-sustained improvement, with flares reliably occurring when treatment was interrupted.

Where it fits

This paper is squarely about ARM 1 (interferon/JAK-STAT): it documents real-world clinical evidence that a single SAMHD1 loss-of-function genotype drives a spectrum of interferon-associated phenotypes, and that this spectrum is broadly JAK-inhibitor responsive. That's relevant background for the A565T model in two ways. First, it reinforces the core premise that SAMHD1 dysfunction converges on a treatable, IFN-driven axis rather than a single fixed syndrome — supporting the idea that a partial, heterozygous loss-of-function variant like A565T could plausibly sit on a milder point of a similar phenotypic continuum, rather than mapping to one predictable presentation. Second, the "flares on drug holiday" observation is a useful clinical signal that tonic IFN-I signaling, once established, may need continuous suppression — a consideration for any future JAK-inhibitor strategy in A565T-driven disease, since ARM 1 is the arm most likely to respond to that class of drug.

Caveats

These are homozygous, complete/near-complete loss-of-function cases (classic AGS5 genetics), not the heterozygous, partial loss-of-function scenario modeled for A565T — phenotype severity and mechanism may not translate directly.
This is a case series (n=3) with retrospective chart review; it establishes association between genotype, phenotype, and drug response, not mechanistic proof of the ANKIB1 node, VDAC1/mitophagy, or NLRP3 pathways.
No mitochondrial (ARM 2) or nucleotide/inflammasome (ARM 3) biomarkers were assessed — the paper speaks only to interferon pathway involvement and clinical JAK-I response, not to whether JAK-resistant arms are active in these or other SAMHD1 patients.

What to watch

The obvious next question is why one genotype produces such different organ-system phenotypes — modifier genes, stochastic ISG thresholds, or differential engagement of the mitochondrial/NLRP3 arms are all plausible explanations worth testing. For A565T specifically, it raises the question of whether heterozygous partial loss-of-function carriers show a similarly broad — if quieter — phenotypic range, and whether JAK-inhibitor responsiveness tracks with how much of the phenotype is ARM-1-driven versus ARM-2/3-driven.

Source: One mutation, divergent journeys: expanding the clinical spectrum of homozygous SAMHD1 deficiency in childhood — 2026.

July 9, 2026
in Weekly Digest, cGAS-STING, treatment-target, NF-kB, NLRP3
51 min read

SAMHD1 Research Digest — 2026-07-09

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 28 papers evaluated | 2 high-relevance (≥7) | 16 medium (5–6) | 10 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Hypoxia synergizes cGAS-STING activation and AKT1 phosphorylation to drive pulmonary inflammation in one-lung ventilation: therapeutic attenuation by RU.521 and MK2206 (from Pulmonology/anesthesiology (one-lung ventilation, acute lung injury))
Jiangsheng Zhang; Yuntao Zou; Dongni Chen; Jiayang Fan; Biying Men — Journal of Inflammation (London, England) 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates cGAS-STING activation via mitochondrial/DNA damage under hypoxic stress, with AKT1-TBK1-IRF3-NF-κB signaling and pharmacological inhibition (RU.521/MK2206), directly modeling the BLUE-stream mechanism and NF-κB crosstalk relevant to the interferon-mitochondrial syndrome, though not SAMHD1-specific.
DOI: 10.1186/s12950-026-00498-6

STING inhibition and BD1-selective BET blockade limit ischemia-reperfusion-induced hepatic tissue remodeling by suppressing pro-inflammasome signaling. (from Hepatology/surgery (ischemia-reperfusion injury))
Adel I. Alalawy; Rabab S. Hamad; Abdulrahman Alasmari; Rehab F. Al-Massabi; Yasm — Tissue & cell 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, mito-ROS-NF-kB, treatment-target

This paper demonstrates cGAS-STING/mtDNA-driven NF-κB and inflammasome activation converging on a druggable checkpoint (STING inhibitor + BET/BRD4 inhibitor), directly paralleling the BLUE/PURPLE loops and NF-κB priming axis in the SAMHD1 mechanism, and implicates hepatology as a relevant clinical bridge.
DOI: 10.1016/j.tice.2026.103387

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Glucocorticoids-Driven Mitochondrial GR Translocation Promotes Heat Stress-Induced Mastitis via the mtDNA-cGAS-STING-NF-κB/NLRP3 Pathway. (from veterinary medicine/dairy science)
He Yuhong; Zhou Zeming; Wei Xin; Su Nier; Yang Tingting — Free radical biology & medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, other

This veterinary study demonstrates mtDNA release triggering cGAS-STING-NF-κB/NLRP3 inflammatory activation via mitochondrial GR translocation, mechanistically paralleling the BLUE/PURPLE loops and NF-κB-NLRP3 crosstalk in the SAMHD1 disease model despite a different upstream trigger (heat stress/glucocorticoids vs. dNTPase deficiency).
DOI: 10.1016/j.freeradbiomed.2026.07.013

Ajugol attenuates acute gouty arthritis by enhancing mitophagy to suppress chondrocyte pyroptosis. (from Rheumatology/pharmacognosy (gouty arthritis and traditional medicine compound screening))
Zhang Yang; Liu Yi; Xie Weiping; Fu Yingqiang; Liu Zhonghao — Biochimica et biophysica acta. Molecular basis of disease 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, mTOR-lysosomal, treatment-target

This paper demonstrates MSU crystal-induced NLRP3 activation and pyroptosis via PINK1/Parkin mitophagy blockade and PI3K/AKT/mTOR signaling, directly paralleling the GOLD stream (dGTP→uric acid→MSU→NLRP3) and mitophagy dysfunction mechanisms in the SAMHD1 model, with a natural compound therapeutic angle.
DOI: 10.1016/j.bbadis.2026.168320

The role of mitochondrial proteases in inflammation and immunity. (from Mitochondrial biology/protein quality control)
Ferreira Anna Rebeka Oliveira; Day Emily A — 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target, other

This review on mitochondrial protein quality control proteases (CLPXP, LONP1, OMA1, AAA-proteases) and their roles in ROS production, mtDNA damage signals, and NLRP3/inflammatory pathway regulation is mechanistically adjacent to the ox-mtDNA/NLRP3/mito-ROS-NF-kB axes central to the SAMHD1 interferon-mitochondrial syndrome, though it does not address SAMHD1, cGAS-STING, or ISG15 directly.
DOI: 10.3389/fimmu.2026.1761658

Lower mitochondrial DNA abundance in blood cells is associated with higher general morbidity and all-cause mortality: a 30-year prospective epidemiological study (from epidemiology/preventive medicine)
A. Sébe; J. Lautaoja-Kivipelto; J. Jokelainen; J. Vaananen; S. Skarp — 2026
Score: 6/10 | Pathways: POLG-mtDNA, NLRP3, treatment-target, clinical-phenotype

Low blood mtDNA abundance linked to chronic low-grade inflammation/innate immunity and all-cause mortality supports the mechanistic link between mitochondrial dysfunction (ox-mtDNA, POLG stalling, NLRP3 priming) and systemic morbidity relevant to the SAMHD1 interferon-mitochondrial syndrome, though it lacks any direct SAMHD1 or cGAS-STING mechanistic data.
DOI: 10.64898/2026.02.10.26345983

Metabolic control of immunity and inflammation: Mitochondrial dynamics, pharmacological targets, and therapeutic opportunities. (from immunometabolism/pharmacology)
Chunling Wang; Wangzheqi Zhang; Yue Shu; Lizhou Song; Yiwen Wan — Pharmacological research 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target, other

This broad review on mitochondrial dynamics in immunometabolism and inflammation touches generally on mitochondria-ROS-NLRP3-NF-kB crosstalk relevant to the mitochondrial-interferon convergence mechanism but lacks specific SAMHD1, cGAS-STING, or dNTP pathway detail.
DOI: 10.1016/j.phrs.2026.108194

Glycosylation as a dynamic regulator of RLR and cGAS-STING innate immune signalling pathways (from Glycobiology)
Jie Tong; Wuchao Zhang; Mengzhou Xue; Chunfu Zheng — Communications Biology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Reviews glycosylation-based regulation of STING stability and cGAS-DNA binding/IRF3/NF-κB signaling, mechanistically upstream of the BLUE/RED loops central to this SAMHD1 interferonopathy model and pointing to novel enzymatic drug targets.
DOI: 10.1038/s42003-026-09767-9

Electroacupuncture Attenuates Neuroinflammation and Postoperative Cognitive Dysfunction in Aged Rats by Suppressing the cGAS–STING Pathway (from Anesthesiology/Neurology (acupuncture and postoperative cognitive dysfunction))
Baobao Ma; Shiwen Fan; Jiaojiao Deng; Kaihua Wei; Yan Li — Experimental Neurobiology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates cGAS-STING-NF-kB-IL-1β neuroinflammatory axis activation and pharmacological/non-pharmacological suppression in a rodent model, mechanistically relevant to the IFN-mitochondrial pathway though not SAMHD1-specific and in a different (surgical/neuroinflammation) context.
DOI: 10.5607/en25042

Targeting VPS4 elicits STING-driven anti-tumor immunity to suppress rhabdomyosarcoma growth (from Oncology (rhabdomyosarcoma tumor immunology/ESCRT biology))
Ray Zhang; Longgui Chen; Xinwen Liang; Jiawen Zhang; Kouta Hamamoto — Oncogene 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, other

Demonstrates cytoplasmic mtDNA-driven cGAS-STING-TBK1-IRF3 activation and NF-κB induction upon VPS4 inhibition, mechanistically paralleling the BLUE loop (VDAC1/mtDNA release to cGAS-STING) and its NF-κB crosstalk, though in an oncology rather than SAMHD1 context.
DOI: 10.1038/s41388-026-03800-1

Bridging innate immunity and iron-dependent death: the interplay between cyclic GMP–AMP synthase–stimulator of interferon genes nexus and ferroptosis in cancer and inflammation (from oncology/cell death biology)
Xin-Xin Chen; Yunxuan Hou; Xinxin Chen; Qi Zhou; Xiang Wang — Frontiers in Cell and Developmental Biology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Reviews cGAS-STING pathway crosstalk with ferroptosis and NF-κB, relevant to core interferon-mitochondrial mechanism though focused on cancer/ferroptosis rather than SAMHD1-specific biology.
DOI: 10.3389/fcell.2026.1766502

Non-genotoxic transplantation and in vivo selection through epitope editing. (from hematology/gene therapy)
Casirati Gabriele; Cosentino Andrea; Freschi Marta; Zeng Jing; Mucci Adele — Nature 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes base/prime editing and epitope-editing strategies for HSPC transplantation and hemoglobinopathy correction, representing a relevant gene-editing delivery advance in myeloid/immune progenitor cells but not directly addressing SAMHD1 or interferon-mitochondrial pathways.
DOI: 10.1038/s41586-026-10737-8

Spiperone targets HBV cccDNA via ER stress–induced innate immune activation and epigenetic silencing (from Hepatology/virology (antiviral drug repurposing for chronic hepatitis B))
Junghwa Jang; Ziyun Kim; Eunseo Kim; Jisung Park; Yulim Choi — bioRxiv 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target

This paper demonstrates a mechanistically analogous pathway (mitochondrial stress → oxidized mtDNA release → IFI16-STING-IRF3 → type I IFN) to the BLUE loop in the SAMHD1 model, but in an antiviral HBV context unrelated to SAMHD1 dysfunction.
DOI: 10.64898/2026.03.31.715751

β-catenin-driven innate and metabolic reprograming in macrophages fuel T-cell-dependent inflammation in Toxoplasma gondii infection: implications for therapeutic intervention (from Parasitology/Infectious Disease Immunology)
G. Kumari; Amit Kumar; Rasmiranjan Muduli; Mayami Das; Prithwik Bhowmik — Cell Death & Disease 2026
Score: 5/10 | Pathways: NLRP3, POLG-mtDNA, ISG15-mitophagy, mito-ROS-NF-kB

This paper demonstrates ox-mtDNA acting as a HAMP to activate AIM2-NLRP3 inflammasome via mitochondrial ROS and PINK1/PARKIN mitophagy in macrophages—mechanistically parallel to the ox-mtDNA/NLRP3 and mitophagy-block streams in the SAMHD1 model, though in a Toxoplasma infection context rather than SAMHD1 dysfunction.
DOI: 10.1038/s41419-026-08953-1

Innate Immune Recognition During RNA Virus Infection: Molecular Mechanisms —A Review (from Virology/microbiology)
Ruqaya Munther Jalil Ewadh; Noor Hassan Ali Altaie; Saif Jabbar Yasir — Journal of Progressive Medical Sciences 2026
Score: 5/10 | Pathways: cGAS-STING, NF-kB-IKK, other

This general review of innate antiviral sensing (RLR/TLR/NLR, MAVS, IRF3/7, NF-κB, cGAS-STING, inflammasome) covers upstream mechanisms relevant to the IFN-I and NF-κB priming loops implicated in the SAMHD1 A565T syndrome, but contains no SAMHD1-, VDAC1-, or ISG15-specific data and is not disease-specific.
DOI: 10.63939/wfh43b42

IFI16 senses and protects stalled replication forks. (from DNA damage/genome instability and cancer biology (oncology/molecular biology))
A. Gamble; Thomas A. Ward; Otto P G Wheeler; Jessica P. Morris; Caryl M Jones — Molecular cell 2026
Score: 5/10 | Pathways: cGAS-STING, NF-kB-IKK

Describes a cGAS-independent STING→NF-κB inflammatory pathway triggered by replication stress, paralleling the STING/NEMO-NF-κB crosstalk axis relevant to the interferonopathy mechanism though not SAMHD1-specific.
DOI: 10.1016/j.molcel.2025.12.024

RNA-LNP-mediated in vivo prime editing corrects disease phenotypes in a mouse model of citrullinemia type I. (from Gene therapy / genetic medicine (metabolic liver disease))
András Tálas; Eleonora I. Ioannidi; Yanik Weber; Tatjana Haenggi; P. Kulcsár — Science translational medicine 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates in vivo RNA-LNP prime editing correction of a monogenic liver disease, providing a relevant technical precedent for future correction of the heterozygous SAMHD1 A565T missense variant, though it is unrelated to interferon/mitochondrial pathways or hepatocyte (not myeloid/immune) delivery.
DOI: 10.1126/scitranslmed.aec7274

CD117 epitope-shielded hematopoietic stem cell transplantation with toxin-free conditioning and in vivo selection ameliorates β-thalassemia model (from hematology/gene therapy)
Marone Romina; Lepore Rosalba; Paschoudi Kiriaki; Zuin Jessica; Sinopoli Alessan — preprint (preprint) 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates prime editing of human CD34+ HSPCs for epitope engineering to enable toxin-free conditioning, relevant as a myeloid-cell gene correction delivery advance that could inform future SAMHD1 A565T correction strategies but has no direct disease mechanism overlap.
DOI: 10.64898/2026.07.07.736903

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

The neuroprotective effect of eugenol in aluminum chloride-induced Alzheimer's rats: Insights into the role of TLR4/MyD88/NF-kB and NLRP3 inflammasome/gasdermin D signaling pathways. (from Neurology/pharmacology (natural product neuroprotection in toxin-induced neurodegeneration model))
El-Dory Shahenda T; Abd El-Fattah Amal A; Sadik Nermin Abdel Hamid; Elbaz Eman M — Archives of biochemistry and biophysics 2026
Score: 4/10 | Pathways: NLRP3, NF-kB-NLRP3-priming

This is an unrelated toxin-induced Alzheimer's rat model using a natural compound (eugenol) that touches on TLR4/MyD88/NF-kB and NLRP3/GSDMD signaling, which overlaps thematically with the NF-κB-NLRP3 priming axis in the disease profile but has no connection to SAMHD1, interferon signaling, or mitochondrial dNTP mechanisms.
DOI: 10.1016/j.abb.2026.110885

Mechanisms and biomarkers of immune checkpoint inhibitor-associated myocarditis: from T cell imbalance to multicellular crosstalk (from Cardio-oncology/immunotherapy toxicity)
Jiawang Huang; Xiuli Xu; Yucheng Jin; Liping Qiao; Heng Yu — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

The paper implicates cGAS-STING and STAT1/NF-κB-driven macrophage polarization in ICI-myocarditis, overlapping mechanistically with the interferon-NF-κB axis but in an unrelated oncologic/autoimmune cardiotoxicity context rather than SAMHD1 biology.
DOI: 10.3389/fimmu.2026.1752354

Ligustilide activates cGAS-STING to chemoprevent tobacco carcinogen-induced lung tumorigenesis. (from Oncology/pulmonology and traditional Chinese medicine pharmacology)
Caisheng Huang; Yanni Tian; Yonghu Chen; Yijia Su; Qiang Fu — International immunopharmacology 2026
Score: 4/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This paper demonstrates cGAS-STING pathway activation (via TBK1-IRF3/NF-κB) as a chemopreventive mechanism in tobacco-induced lung cancer, sharing core pathway machinery with the SAMHD1 syndrome but in an unrelated oncologic/pharmacologic context with no SAMHD1 or mitochondrial dNTP connection.
DOI: 10.1016/j.intimp.2026.117043

Co-exposure to cannabinoids and nicotine increases senescence in prenatal human lung development. (from Pediatric pulmonology/prenatal toxicology)
El Alam Imad; Belgacemi Randa; Hoarau Antony; Le Saux Claude Jourdan; Glass Ian — Pediatric research 2026
Score: 3/10 | Pathways: pregnancy-fetal, other

Paper shows DNA damage-induced senescence with secondary interferon pathway activation (MX1/IFI2) and SASP in fetal lung explants, a tangential mechanistic parallel to the interferon-mitochondrial axis but not involving SAMHD1, cGAS-STING, NLRP3, or the core disease pathways.
DOI: 10.1038/s41390-026-05037-w

CRISPR Cas9 revolutionizing genetic engineering and therapeutic applications. (from biotechnology/genetic engineering)
Durairaj Sivakumar; Durairaj Shankar; Krishnan Sundar; Raju Anand — Journal of biotechnology 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General CRISPR-Cas9 review covering broad therapeutic applications with only superficial mention of base/prime editing, lacking any SAMHD1, interferonopathy, or immune-cell-specific delivery focus relevant to this disease profile.
DOI: 10.1016/j.jbiotec.2026.06.012

Orchestrating the gut microbiota–mitochondrial–immune axis in gynecological diseases: mechanisms and dual-targeting therapeutic strategies (from Gynecology/gut microbiota research)
Haixia Tang; Yiting Zhang; Yanting Wang; Ze Zhou; Rong Sun — Frontiers in Reproductive Health 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, other

This gynecology-focused review touches cGAS-STING/NLRP3 and mitochondrial pathways generically via gut microbiota axis, but has no connection to SAMHD1, interferonopathy mechanism, or family phenotypes.
DOI: 10.3389/frph.2026.1845581

NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration (from Orthopedics/Rheumatology (osteoarthritis))
Peng Wan; Yimin Zheng — Frontiers in Immunology 2026
Score: 3/10 | Pathways: NF-kB-IKK, other

This is a general osteoarthritis review on NF-κB integrating mechanical stress and innate immunity, mentioning mitochondrial DNA sensing and DAMPs but with no connection to SAMHD1, cGAS-STING/NLRP3 interferonopathy mechanisms, or any documented family phenotype.
DOI: 10.3389/fimmu.2026.1842443

Zinc-Iron Bimetallic MOF-Integrated Thermosensitive Hydrogel for Breast Cancer Immunotherapy via Ferroptosis-Induced cGAS–STING Activation (from Oncology/Biomaterials engineering)
Yihao Zhan; Xiangyan Chen; Yantao Li — BIO Web of Conferences 2026
Score: 3/10 | Pathways: cGAS-STING, other

While it engages the cGAS-STING pathway, this is an engineered nanomaterial oncology therapeutic for breast cancer immunotherapy unrelated to SAMHD1 mechanism, mitochondrial dNTP dysregulation, or the interferon-mitochondrial syndrome described.
DOI: 10.1051/bioconf/202623703015

Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways (from Gastroenterology/Oncology (microbiome-driven colorectal carcinogenesis))
Asma Bachir; A. Altaie; Riyad Bendardaf; Iman M. Talaat; R. Hamoudi — Frontiers in Microbiology 2026
Score: 3/10 | Pathways: cGAS-STING, NF-kB-IKK, other

This paper discusses cGAS-STING and NF-κB signaling in the context of colorectal cancer driven by microbial dysbiosis, sharing pathway components but in an unrelated disease mechanism (bacterial genotoxicity, not SAMHD1 dNTPase dysfunction or interferonopathy syndrome).
DOI: 10.3389/fmicb.2026.1795882

Abstract PS4-04-18: Direct targeting of amplified HER2 gene activates immune signaling through DNA damage response (from Oncology (breast cancer therapeutics))
A. Krysztofiak; A. Brown; A. Minnah; F. Rogers — Clinical Cancer Research 2026
Score: 3/10 | Pathways: cGAS-STING

Discusses cGAS-STING activation via DNA damage in HER2+ breast cancer, tangentially touching a core pathway but unrelated to SAMHD1 mechanism or family phenotypes.
DOI: 10.1158/1557-3265.sabcs25-ps4-04-18

Pathway Coverage This Week

cGAS-STING: 16 papers
treatment-target: 13 papers
NF-kB-IKK: 12 papers
NLRP3: 10 papers
other: 10 papers
mito-ROS-NF-kB: 5 papers
prime-editing: 4 papers
gene-therapy-delivery: 4 papers
NF-kB-NLRP3-priming: 2 papers
POLG-mtDNA: 2 papers
urate-NLRP3: 1 papers
mTOR-lysosomal: 1 papers
clinical-phenotype: 1 papers
ISG15-mitophagy: 1 papers
pregnancy-fetal: 1 papers

↩ Re-run 08:44 UTC | Model: claude-sonnet-5

Summary: 111 new papers | 14 high-relevance (≥7) | 45 medium (5–6) | 52 low (3–4)

🔴 High Relevance

cGAS inhibitor IMSB301 modifies interferon signalling in peripheral mononuclear cells of SAMHD1 genetic interferonopathy in vitro (from Clinical immunology/translational rare disease genetics (AGS))
V. Han; J. Hayes; Lijun Sun; Teresa Mooneyham; Michelle Lorentzos — Clinical & Translational Immunology 2026
Score: 9/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype

Directly demonstrates SAMHD1-mutation-driven interferon signature (IFIT1/IFIT3/IFI44L/ISG15/OAS1) and its reversal by the cGAS inhibitor IMSB301, a named therapeutic candidate in the mechanism list, providing direct in vitro validation of the BLUE loop and a druggable target for SAMHD1 interferonopathy.
DOI: 10.1002/cti2.70090

One mutation, divergent journeys: expanding the clinical spectrum of homozygous SAMHD1 deficiency in childhood (from Pediatric rheumatology)
Hulya Ercan Emreol; Dilara Ünal; D. Ayvaz; Y. Bilginer; S. Özen — Rheumatology (Oxford, England) 2026
Score: 9/10 | Pathways: AGS-spectrum, JAK-STAT, cGAS-STING, clinical-phenotype, treatment-target

Directly demonstrates SAMHD1 loss-of-function mutation causing a spectrum of interferonopathy phenotypes (myopathy, panniculitis, lupus-like disease) responsive to JAK inhibition, reinforcing the core interferon-driven mechanism and phenotypic heterogeneity relevant to the family's diverse presentations.
DOI: 10.1093/rheumatology/keaf695

Self-assembled nanoparticles from Xiexin Decoction attenuate ulcerative colitis by targeting VDAC1-Mediated NLRP3 inflammasome activation (from gastroenterology/nanomedicine (traditional Chinese medicine-derived nanotherapeutics for ulcerative colitis))
Zheng Chu; Tong Yang; Ying Zhang; Qianru Zhu; Dawei Wang — Materials Today Bio 2026
Score: 7/10 | Pathways: VDAC1, NLRP3, treatment-target

Demonstrates that VDAC1 oligomerization inhibition blocks oxidized mtDNA release and NLRP3 activation, directly validating the BLUE pathway mechanism and identifying a druggable VDAC1-targeting compound (berberine) relevant to the family's inflammasome-driven phenotype.
DOI: 10.1016/j.mtbio.2026.103078

Mitochondrial DNA drives NLRP3-IL-1β axis activation in microglia by binding to NLRP3, leading to neurodegeneration in Parkinson’s disease models (from Neurology/Parkinson's disease research)
Qinglin Gan; Xiaolong Fu; T. Zhou; Naiyu Fan; Nan Nan — Cell Death & Disease 2026
Score: 7/10 | Pathways: NLRP3, POLG-mtDNA, treatment-target

Demonstrates ox-mtDNA directly binding and activating NLRP3 in microglia (Loop B mechanism), reinforcing the PURPLE/NLRP3 pathway with a novel molecular mechanism relevant to neuroinflammation, though not SAMHD1-specific.
DOI: 10.1038/s41419-026-08424-7

Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction (from Cardiology (HFpEF))
Xingwei Zhao; Shengyu Huang; Qiuling Li; Yang Yu; Chunxiang Zhang — Frontiers in Immunology 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, NF-kB-NLRP3-priming, clinical-phenotype, other

Describes mtDNA release-driven cGAS-STING/TLR9-NLRP3 inflammatory amplification loops closely mirroring the BLUE/Loop A/B mechanisms, relevant to potential cardiac comorbidity in the interferon-mitochondrial syndrome though not SAMHD1-specific.
DOI: 10.3389/fimmu.2026.1866184

Oxidized mtDNA Contributes to Pulmonary Inflammation and Fibrosis in Bleomycin‐Induced Lung Injury (from Pulmonology)
Ye Mao; Xinyu Tian; Jiayuan Ai; Xiaoting Zhou; Yanghong Ni — MedComm 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target

Demonstrates oxidized mtDNA driving STING- and NLRP3-dependent inflammation and fibrosis, directly validating the PURPLE/BLUE convergent mechanism (ox-mtDNA -> cGAS-STING and NLRP3) central to the SAMHD1 interferon-mitochondrial syndrome, though in a lung fibrosis model rather than SAMHD1 context.
DOI: 10.1002/mco2.70664

The Autophagy–Inflammation Axis in Kawasaki Disease: Pathogenic Mechanisms and Translational Opportunities (from Pediatric cardiology/rheumatology (Kawasaki disease vasculopathy))
Qiang Xu; Yali Wu; Yan Ding — Journal of Clinical Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, mTOR-lysosomal, treatment-target

Describes mitophagy/lysosomal dysfunction driving mtDNA release, NLRP3 and cGAS-STING activation in a pediatric vasculitis, directly paralleling the family's mitochondrial-interferon-inflammasome mechanism and mTOR/rapamycin therapeutic angle.
DOI: 10.3390/jcm15103918

Mitochondrial Calcium Overload Drives mtDNA-cGAS-STING Activation via VDAC1 and MCU Upregulation in Periodontitis (from Dentistry/Periodontology)
Xinyi Cheng; Yu Cai; Yiran Geng; Xiaoying Zang; Jia Liu — International Journal of Molecular Sciences 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target

This paper mechanistically validates the VDAC1-mediated mtDNA leakage → cGAS-STING activation axis (Loop A/BLUE pathway) central to the SAMHD1 syndrome model, even though studied in a different inflammatory disease context.
DOI: 10.3390/ijms27104317

Less severe alcoholic injury in cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) deficient mice, a possible impact of intracellular DNA recognition. (from Hepatology/alcoholic liver disease)
T. Bhunyakarnjanarat; Chatsuree Suksamai; Kollawat Somsri; Kamollada Kowitwibool — International immunopharmacology 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

Demonstrates cGAS-dependent cytosolic mtDNA sensing driving NF-κB/IL-1β inflammation and mitochondrial oxidative injury in a liver disease model, directly reinforcing the BLUE-pathway mechanism (VDAC1/mtDNA-cGAS-STING) central to the SAMHD1 interferon-mitochondrial syndrome and its hepatology relevance to the family's hepatic steatosis phenotype.
DOI: 10.1016/j.intimp.2026.116875

Lead exposure acts as a risk factor of PCOS development via SOD2-mediated mtDNA leakage. (from Reproductive endocrinology/toxicology)
Qiao-ling Zhang; Yinfei Xing; Shijie Li; Zhanqing Yang; Baiyu Li — Chemico-biological interactions 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

This paper demonstrates mtDNA leakage via permeability transition pore triggering cGAS-STING-TBK1-NF-κB signaling driven by mitochondrial oxidative stress, closely paralleling the BLUE/NF-κB crosstalk mechanisms central to the SAMHD1 syndrome despite a different upstream trigger (lead exposure) and disease context (PCOS).
DOI: 10.1016/j.cbi.2026.112075

Interferon-alpha selectively signals mitochondrial pore opening to allow mitochondrial RNA release in systemic lupus erythematosus: pathophysiological implications (from Rheumatology (SLE))
Chuan-Yueh Huang; De-Wei Wu; L. Hung; Chien-Hsiang Wu; Shue-Fen Luo — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: VDAC1, cGAS-STING, IRF7-metabolic, clinical-phenotype

Demonstrates IFN-alpha-driven VDAC1-mediated mitochondrial pore opening and nucleic acid (mtRNA) release in macrophages, directly paralleling the BLUE loop VDAC1/cGAS-STING mechanism central to the SAMHD1 interferonopathy model, though in an SLE rather than SAMHD1 context.
DOI: 10.1186/s12964-026-02910-3

Janus Kinase Inhibitors in Treatment of Primary Immune Regulatory Disorders. (from Clinical allergy/immunology (JAK inhibitor therapeutics for inborn errors of immunity))
N. Alsaati; L. Satter — The journal of allergy and clinical immunology. In practice 2026
Score: 7/10 | Pathways: JAK-STAT, treatment-target, AGS-spectrum, clinical-phenotype

Reviews JAK inhibitor use in type I interferonopathies and immune dysregulation disorders, directly relevant as a therapeutic strategy applicable to the IFN-I-driven SAMHD1 haploinsufficiency syndrome described.
DOI: 10.1016/j.jaip.2026.05.019

Beyond the interferon score: neurofilament light chain and glial fibrillary acidic protein capture immune-mediated neuroinjury and response to JAK inhibition in Aicardi–Goutières syndrome (from Neurology/biomarker science)
L. Wege; Christian Klemann; Sandy Siegert; Annette E Bley; S. Koss — Frontiers in Immunology 2026
Score: 7/10 | Pathways: AGS-spectrum, JAK-STAT, treatment-target, clinical-phenotype

AGS is the core type I interferonopathy prototype in the SAMHD1 mechanistic spectrum, and this paper demonstrates JAK inhibitor efficacy on neuroinjury biomarkers (pNfL/pGFAP) that outperform IFN score, directly relevant to treatment monitoring strategies applicable to SAMHD1-driven interferonopathy.
DOI: 10.3389/fimmu.2026.1782352

Intranasal Human NSC‐Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS‐STING Signalling, in Aged Hippocampus (from Neuroscience/regenerative medicine (stem cell-derived extracellular vesicle therapeutics for neuroinflammaging))
L. N. Madhu; Maheedhar Kodali; Shama Rao; Sahithi Attaluri; Raghavendra Upadhya — Journal of Extracellular Vesicles 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, treatment-target, NF-kB-NLRP3-priming

This paper demonstrates a therapeutic EV-based approach that suppresses NLRP3 inflammasome and cGAS-STING-IFN-1 signaling via specific miRNAs, directly relevant to the convergent interferon-inflammasome mechanism underlying the SAMHD1 syndrome even though it is in an aging-neuroinflammation rather than SAMHD1 context.
DOI: 10.1002/jev2.70232

🟡 Medium Relevance

Mitochondrial Regulation of the NLRP3 Inflammasome in Diabetic Kidney Disease: From Mechanisms to Therapeutic Strategies (from Nephrology/Endocrinology)
Xiangyun Chen; Zhenyu Wu; Kaiyan Yu; Juan Zhang; Hongjie Di — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Reviews mitochondrial ROS/ox-mtDNA-driven NLRP3 activation as a core mechanistic parallel to Loop B/mito-ROS-NF-kB axes, though contextualized in diabetic kidney disease rather than SAMHD1 interferonopathy.
DOI: 10.3390/ijms27114819

Icariin attenuates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome through SIRT3-mediated TFAM deacetylation (from Cardiology/pharmacology)
Mingsheng Sun; Hui Huang; Chao Wei; Yuan Xing; Bing Wu — Frontiers in Pharmacology 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates mtROS/cytosolic mtDNA-driven NLRP3 activation in cardiomyopathy and its pharmacological reversal via SIRT3-TFAM, paralleling the PURPLE/mito-ROS-NF-kB loop implicated in the SAMHD1 syndrome's cardiac and mitochondrial pathology.
DOI: 10.3389/fphar.2026.1829772

PPARG activation by pioglitazone promotes mitophagy and inhibits the NLRP3 inflammasome to alleviate arthritic joint inflammation and bone damage. (from Rheumatology/endocrinology (thiazolidinedione repurposing for RA-T2DM multimorbidity))
Tingting Fu; Yanglin Wu; Bo Wang; Qin Zhang; Lujun Guo — Autophagy 2026
Score: 6/10 | Pathways: NLRP3, ISG15-mitophagy, treatment-target, clinical-phenotype

Demonstrates that mitophagy induction (via PPARG) suppresses NLRP3 inflammasome activation and IL1B/IL18 release in arthritis, directly relevant to the family's RA phenotype and the mitophagy-block/NLRP3 axis central to the SAMHD1 syndrome, though it does not involve interferon or SAMHD1 mechanisms.
DOI: 10.1080/15548627.2026.2676071

Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases (from Neurodegeneration/mitochondrial bioenergetics)
Salvatore Nesci — Biomedicines 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target

Reviews mtDNA-driven ROS/cGAS-STING/NLRP3 neuroinflammatory crosstalk analogous to the PURPLE/BLUE loops but centers on ETC supercomplex biology in neurodegeneration rather than SAMHD1 dNTPase mechanism.
DOI: 10.3390/biomedicines14030682

Mitochondrial dysregulation in rheumatoid arthritis: From pathogenic mechanisms to therapeutic innovations. (from Rheumatology)
Ao Wang; Tiangang Ma; Jinyan Yu; Yanbing Hu; Xin Di — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, clinical-phenotype

Reviews mitochondrial dysfunction driving NLRP3/cGAS-STING activation in rheumatoid arthritis, directly relevant to the family's RA phenotype and the interferon-mitochondrial mechanism, though not SAMHD1-specific.
DOI: 10.1016/j.intimp.2026.116622

Subthreshold Thermal Stress Aggravates Methamphetamine-Induced Cardiomyocyte Pyroptosis via the Mitochondrial ROS/BAX/mtDNA/NLRP3 Pathway (from toxicology/cardiology (methamphetamine-induced cardiotoxicity))
Mengmeng Wang; Cong-Cong Hou; Mengliang Hu; Dan Zhou; Xintao Wang — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates a mitochondrial ROS/BAX/mtDNA-driven NLRP3 inflammasome activation pathway causing pyroptosis, directly paralleling the disease's ox-mtDNA/NLRP3 mechanism and mitochondrial-targeted antioxidant therapeutic strategy, though in a toxicology rather than SAMHD1 context.
DOI: 10.3390/ijms27115000

Ag2Se quantum dots neurotoxicity: mitochondrial stress drives ferroptosis-dependent microglial inflammation (from nanotoxicology/environmental health)
Yongshuai Yao; Zhihui Wang; Chunhui Zhang; Xiaoquan Huang; T. Wei — Journal of Nanobiotechnology 2026
Score: 6/10 | Pathways: NLRP3, cGAS-STING, mito-ROS-NF-kB

This nanotoxicology paper demonstrates mtROS-mPTP-mtDNA leakage-STING-NLRP3 ferroptosis axis, mechanistically paralleling the BLUE/PURPLE loop convergence on NLRP3 via mitochondrial damage even though triggered by quantum dots rather than SAMHD1 deficiency.
DOI: 10.1186/s12951-026-04322-4

The mitochondrial logic of inflammaging: how energy imbalance drives fibroblast SASP and tissue-specific aging (from Dental/periodontal biology and aging/senescence research)
Yu Huan; Qiqi Wang; Rongkaixuan Fang; Yue Sun; Meiya Suo — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

Describes mitochondrial danger signals (mtROS, mtDNA) converging on cGAS-STING, NLRP3, and NF-kB to drive SASP/inflammaging, mechanistically overlapping with the SAMHD1 interferon-mitochondrial loops though not disease-specific.
DOI: 10.3389/fimmu.2026.1881243

Trihexyl phosphate exposure disrupts mitophagy and activates mtDNA-cGAS-STING signaling to drive pyroptosis and steroidogenic impairment in Leydig cells. (from Toxicology/Andrology (reproductive endocrinology))
Yinwei Dai; Zhuoqi Chen; Weijian Zhu; Shaowei Wang; X. Ren — Journal of hazardous materials 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

This paper demonstrates the mitophagy-mtDNA-cGAS-STING-NLRP3-pyroptosis cascade in a toxicological (reproductive) context, mechanistically paralleling the BLUE/RED loops in the SAMHD1 syndrome despite lacking any SAMHD1 or genetic haploinsufficiency link.
DOI: 10.1016/j.jhazmat.2026.141827

Programming Mn(II) coordination in self-assembling peptides amplifies mtDNA-driven STING signaling for potent antitumor immunity (from Materials science/nanomedicine oncology immunotherapy)
Guoyu Xia; Chenyang Wang; L. Peng; Weiyu Xing; Lulu Wang — Materials Today Bio 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

This paper demonstrates a nanomaterial-driven mtDNA leakage → cGAS-STING amplification mechanism analogous to the BLUE pathway (VDAC1/mtDNA-cGAS-STING) in the syndrome, though applied here as an antitumor immunotherapy strategy rather than disease mechanism.
DOI: 10.1016/j.mtbio.2026.103373

Metformin attenuates lens epithelial cell senescence by suppressing cGAS-STING via SIRT1-PGC-1α-mediated mitochondrial fission. (from Ophthalmology (age-related cataract/lens epithelial cell biology))
Jialin Luo; Chaoqun Wei; Liyao Sun; Huirui Liu; Yu Mi — Experimental gerontology 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, treatment-target

Demonstrates mitochondrial fragmentation-driven mtDNA cytosolic release activating cGAS-STING to promote senescence, mirroring the BLUE loop mechanism, with metformin/SIRT1-PGC-1α as a potential upstream treatment lever relevant to the syndrome's core pathway even though outside immunology.
DOI: 10.1016/j.exger.2026.113157

USP10 activity as sensitizer of lung adenocarcinoma to immune checkpoint inhibitors: Upregulating PD-L1 via the ANT3-mediated activation of the cGAS-STING pathway. (from Oncology (lung adenocarcinoma immunotherapy biomarker research))
Aman Wang; Mengyuan Xu; Z. Ning; Yibin Teng; He Qin — Journal of Clinical Oncology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mtDNA leakage-driven cGAS-STING-TBK1-IRF3 activation via a mitochondrial protein (ANT3) that upregulates PD-L1, mechanistically parallel to the VDAC1/mtDNA-cGAS-STING loop in the SAMHD1 model though in an oncology/immunotherapy context rather than interferonopathy.
DOI: 10.1200/jco.2026.44.16_suppl.8542

A Dual‐Function Mitochondria‐Targeted Polyoxometalate Nanomicelle Boosts Pyroptosis‐Dependent Antitumor Immune Response in Triple‐Negative Breast Cancer (from Oncology/nanomedicine (breast cancer immunotherapy))
Qingqing Dou; Peixiao Jiang; Fang Zhang; Kun Yang; Zhichao Li — Rare Metals 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mTOR-lysosomal, treatment-target

While focused on TNBC oncology rather than SAMHD1 biology, this paper demonstrates the exact core mechanism in the disease profile (GSDMD-mediated mtDNA release → cGAS-STING activation, mitophagy blockade sustaining the mtDNA-cGAS-STING axis) via a nanomaterial approach, offering mechanistic insight and a potential therapeutic strategy (lysosomal/autophagy blockade to amplify interferon signaling) relevant to the convergent interferon-mitochondrial syndrome pathways.
DOI: 10.1002/rar2.70302

C62-25 From Lupus to Interferonopathy: Revisiting the Diagnosis in a Child With Interstitial Lung Disease (from Pediatric Pulmonology/Critical Care Medicine)
A. Kenney; C. Spencer Grant; S. Shea — American Journal of Respiratory and Critical Care Medicine 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, IRF7-metabolic

USP18-related type I interferonopathy presenting with ILD, NAFLD, and intracranial calcifications closely parallels the IFN-I/AGS-spectrum overlap and multi-organ interferonopathy phenotype relevant to SAMHD1-driven disease, though it involves a different gene in the same pathway.
DOI: 10.1093/ajrccm/aamag162.2768

Leveraging Type I Interferons: Exploring Pathogenesis and Therapeutic Strategies in Autoimmune Diseases. (from Rheumatology/autoimmune disease)
Sarvin Jabbari; R. Safaralizadeh; E. A. V. Beilankouhi; Mohammad Valilo; Mohamma — Critical reviews in immunology 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, treatment-target

General review of type I interferon signaling, epigenetics, and JAK-STAT in autoimmune disease/interferonopathies is relevant background to the IFN-I arm of the SAMHD1 mechanism but does not address SAMHD1, mitochondrial dNTP handling, or inflammasome crosstalk directly.
DOI: 10.1615/critrevimmunol.2026062673

Anifrolumab, a potential treatment for ADA2 deficiency. (from Rheumatology)
L. Vincenti; Jonathan Sormani; Alexandre Belot; Maël Richard; Yoann Roubertou — RMD open 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype, AGS-spectrum

DADA2 is a related monogenic interferonopathy with autoinflammatory/vasculitis features showing successful IFN-I receptor blockade (anifrolumab), directly relevant as a treatment-target precedent for SAMHD1-driven interferon pathway pathology.
DOI: 10.1136/rmdopen-2025-006569

PTPN1-related autoinflammation is a common cause of Aicardi-Goutières Syndrome with reduced penetrance (from Genetics/genomics (AGS gene discovery cohort))
D. Calame; Emma Wiener; F. Gavazzi; A. Sevagamoorthy; A. Pizzino — medRxiv 2026
Score: 6/10 | Pathways: AGS-spectrum, cGAS-STING, JAK-STAT, clinical-phenotype

PTPN1 is a novel AGS-spectrum interferonopathy gene with reduced penetrance and later-onset autoinflammatory phenotype, directly analogous to the SAMHD1 A565T haploinsufficiency model of variable-penetrance type I interferonopathy.
DOI: 10.64898/2026.03.27.26345228

Severe Hyperinflammation and Evans Syndrome in Patient with RelA Deficiency Successfully Treated with Infliximab (from Rheumatology/Immunology (inborn errors of immunity))
Jamie Loutfy; Michell M Lozano; Sanjay J. Shah — Journal of Human Immunity 2026
Score: 6/10 | Pathways: NF-kB-IKK, treatment-target, clinical-phenotype, AGS-spectrum

RelA (p65) deficiency directly implicates the NF-kB pathway central to this disease's crosstalk axis, causing hyperinflammation/interferonopathy-like features and MAS treated with anti-TNF, offering therapeutic and mechanistic parallels though not SAMHD1-specific.
DOI: 10.70962/cis2026abstract.187

Haploinsufficiency for Human ABCF1 Underlies Gastrointestinal Autoimmunity (from Gastroenterology/immunogenetics (celiac disease and IBD genetics))
Xin Long; Xi Li; Zhikai Chi; W. Ying; Hemanth Karnati — Journal of Human Immunity 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

This paper describes another heterozygous haploinsufficiency gene (ABCF1) causing constitutive interferon signaling, JAK-STAT hyperactivation, and autoimmune/GI inflammation responsive to JAK inhibition (tofacitinib), closely paralleling the interferonopathy mechanism and treatment strategy relevant to SAMHD1 A565T.
DOI: 10.70962/cis2026abstract.213

Mechanisms outpacing medicine in autoinflammatory diseases (from clinical rheumatology/genetic medicine treatment strategy)
Ruyue Chen — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, treatment-target, clinical-phenotype, NF-kB-IKK, AGS-spectrum

This conceptual review on genotype-informed treatment frameworks for interferonopathies, inflammasomopathies, and NF-kB disorders provides directly relevant therapeutic decision-making context for the SAMHD1 A565T interferon-mitochondrial syndrome, though it lacks SAMHD1-specific data or mitochondrial dNTP mechanism detail.
DOI: 10.3389/fimmu.2026.1868804

Bespoke Base and Prime Editing Approaches for STING-Associated Vasculopathy with Onset in Infancy (SAVI) (from gene therapy / genome editing for inborn errors of immunity)
Enrico Drago; Jona Papri; Chiara Fresia; G. Casirati; F. Schena — Journal of Human Immunity 2026
Score: 6/10 | Pathways: cGAS-STING, prime-editing, gene-therapy-delivery, AGS-spectrum, treatment-target

This paper demonstrates base/prime editing correction of a STING1 gain-of-function interferonopathy mutation, directly relevant as a gene-therapy translation model for the SAMHD1 A565T interferon-driven syndrome, though it targets a different upstream node in the same IFN-I pathway.
DOI: 10.70962/cis2026abstract.5

COPA Syndrome and Its Many Flavors (from clinical immunology/genetics (pediatric inborn errors of immunity))
Faiyza Osman; J. P. Lopes — Journal of Human Immunity 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, treatment-target

COPA syndrome is another monogenic type I interferonopathy with JAK-inhibitor responsiveness, immune dysregulation, and overlapping clinical features (arthralgia, pulmonary disease, autoinflammation) analogous to the SAMHD1 interferon-mitochondrial syndrome, offering cross-disease mechanistic and diagnostic parallels.
DOI: 10.70962/cis2026abstract.133

Influenza a virus NS2 suppresses NFKB/NF-κB signaling to facilitate viral replication by mediating the autophagic-degradation of IKBKG/NEMO. (from Virology/Autophagy biology)
Bo Zhang; Lebin Han; Chenying Cui; Jiaxin Huang; Qiyun Zhu — Autophagy 2026
Score: 6/10 | Pathways: NF-kB-IKK, other

Demonstrates a viral immune-evasion mechanism directly targeting NEMO/IKBKG via autophagic degradation, relevant to the NF-κB/IKK axis and viral-trigger context (adenovirus/SARS-CoV-2) implicated in the family's post-viral ME/CFS onset, though it does not involve SAMHD1 or interferon/NLRP3 pathways directly.
DOI: 10.1080/15548627.2026.2676801

Adenine Nucleotide Translocase: From Nucleotide Carrier to a Modulator of Mitochondrial Bioenergetics, Quality Control, and Cellular Communication (from cardiology/mitochondrial bioenergetics)
U. Rauch-Kroehnert; J. Heger; Ulf Landmesser; A. Dörner — Cells 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, ISG15-mitophagy, mito-ROS-NF-kB, other

ANT is a functional analog/partner to VDAC1 in mitochondrial permeability transition, nucleic acid release, and PINK1-Parkin mitophagy-inflammasome crosstalk, providing mechanistic support for the BLUE/RED loop architecture even without direct SAMHD1 linkage.
DOI: 10.3390/cells15070646

Self-Carrier Nanoagonist Enabling Positive Feedback Regulation of Cuproptosis-Immunity for Potent Antitumor Therapy. (from Oncology/nanomedicine)
Minhao Jiang; Penghui Li; Yinuo Shu; Guoshi Xu; Yinghua Peng — ACS nano 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Describes mtDNA release triggering cGAS-STING activation via mitochondrial damage in a cancer nanomedicine context, mechanistically overlapping with the BLUE pathway's mtDNA-cGAS-STING axis though applied to oncology rather than SAMHD1 interferonopathy.
DOI: 10.1021/acsnano.5c19675

Genotoxicity profiling reveals distinct platform- and cell type–specific effects in therapeutic gene editing for genetic hyperinflammation (from Genome editing / gene therapy (hematology-immunology translational))
L. Lei; M. M. Kaufmann; Jessica P. Lao; Gudrun Thoulass; Sandra Ammann — Cell stem cell 2026
Score: 6/10 | Pathways: gene-therapy-delivery, prime-editing, treatment-target, NLRP3

This paper demonstrates base-editing correction of a point mutation causing a genetic hyperinflammatory syndrome (FHL3) in HSCs/T cells, directly analogous to the gene-correction strategies (base/prime editing in myeloid/immune cells) relevant to future SAMHD1 A565T therapeutic translation, though it does not involve SAMHD1, IFN-I, or NLRP3 mechanistically.
DOI: 10.1016/j.stem.2026.04.014

Galactose-decorated lipid nanoparticle-mediated delivery of a selective NLRP3 inhibitor attenuates hepatic inflammation in metabolic dysfunction-associated steatotic liver disease. (from Materials science/nanomedicine drug delivery)
Chunyan Niu; Wen Gao; M. Tan; Yue Chen; Yongqiang Shi — Journal of materials chemistry. B 2026
Score: 6/10 | Pathways: NLRP3, NF-kB-NLRP3-priming, treatment-target

Uses MCC950 (a known NLRP3 inhibitor referenced in the mechanism profile) with a targeted delivery system to treat NF-κB/NLRP3-driven hepatic steatosis/fibrosis, directly relevant to the GOLD/mito-dNTP-transport hepatic steatosis endpoint and hepatology clinical context.
DOI: 10.1039/d5tb02289d

[211At]Astatine-Based Conditioning with a Humanized CD45 Antibody for Autologous Hematopoietic Stem Cell Gene Therapy. (from Hematology/gene therapy engineering)
S. Radtke; George S. Laszlo; Kyle Swing; Andrea Repele; Jacob W Barton — Blood 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

Describes base editing and HSPC gene therapy delivery methodology relevant to future correction strategies for SAMHD1 variants but does not address SAMHD1 or interferon-mitochondrial mechanisms directly.
DOI: 10.1182/blood.2026033789

LAH5-mediated delivery of prime editor ribonucleoprotein complexes for genome editing. (from gene therapy / bioengineering (cardiology model system))
Bing Yao; Mert Öktem; Geng Yang; Qian Wang; Mark A Daniels — International journal of pharmaceutics 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Describes a non-viral CPP-based delivery system for prime editor RNPs correcting a point mutation, technically relevant as a platform for future correction of SAMHD1 A565T though applied here to a cardiac PLN mutation, not immune/myeloid cells.
DOI: 10.1016/j.ijpharm.2026.126622

Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells (from Biomedical engineering/gene therapy (HSC bioengineering))
Federico Midena; Laura Alessandrini; C. Conci; M. Barcella; Francesco Gazzo — Cell Stem Cell 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

Describes a nanoengineered 3D HSPC culture platform enabling improved base/prime editing and lentiviral gene addition persistence, relevant as a delivery/correction strategy for future SAMHD1 het variant correction in HSC/myeloid lineages but not directly addressing SAMHD1 or its pathways.
DOI: 10.1016/j.stem.2025.12.016

Transduction of quiescent human hematopoietic stem and progenitor cells using lentiviral vectors and virus-like particles (from Gene and cell therapy / hematology)
Denise Klatt; C. Brendel — Current protocols 2026
Score: 5/10 | Pathways: gene-therapy-delivery

Describes lentiviral/eVLP transduction of quiescent HSPCs, a delivery platform relevant to future gene correction strategies for SAMHD1 variants in immune/myeloid cells but does not address disease mechanism directly.
DOI: 10.1002/cpz1.70301

Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters. (from gene therapy/genome engineering)
D. Canarutto; Martina Fiumara; Vigneshwaran Venkatesan; Chiara Gaddoni; Kohei Sh — Nature biotechnology 2026
Score: 5/10 | Pathways: gene-therapy-delivery

Describes an HSPC gene-editing selection/enrichment platform (SMArT) relevant to future correction of het missense variants like SAMHD1 A565T in myeloid/immune progenitor cells, though not disease-specific.
DOI: 10.1038/s41587-026-03142-z

Functional correction and genome integrity with duplex base editing of β-thalassemic hematopoietic stem cells (from Hematology/gene therapy)
Nikoletta Y Papaioannou; Petros Patsali; Julia Klermund; P. Papasavva; G. Andrie — Genome Biology 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

Demonstrates base-editing safety/efficacy in primary CD34+ HSCs for a monogenic disease, methodologically relevant to future SAMHD1 het missense correction strategies in myeloid/immune cells despite different disease target.
DOI: 10.1186/s13059-026-03974-7

Novel gene-editing technologies: applications of CRISPR-Cas9, base editing, and prime editing in SCID gene therapy (from gene therapy/hematology)
Greg Crawford; P. Sagoo; H. B. Gaspar — Journal of Translational Genetics and Genomics 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews CRISPR-Cas9, base editing, and prime editing for SCID HSC gene therapy, relevant as a delivery/correction platform analogous to future SAMHD1 A565T myeloid correction but not disease-specific.
DOI: 10.20517/jtgg.2025.95

Abstract 3019: The first coacervate based delivery system for efficient and safe genetic engineering in stem cells (from gene therapy/bioengineering)
Peipei Zhu; Manman Lu; Qing Zhang; Renxia Zhang; Lihong Jiang — Cancer Research 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

Describes a novel non-viral coacervate delivery platform enabling efficient mRNA/Cas9 RNP and prime editing delivery into HSCs and iPSCs, relevant as a potential future correction strategy for a heterozygous missense variant like SAMHD1 p.A565T though not disease-specific.
DOI: 10.1158/1538-7445.am2026-3019

High-fidelity genome and prime editing enabled by the AI-designed openCRISPR-1. (from genome editing / synthetic biology)
Hye-Yeon Hwang; Hwalin Yi; Yuju Gwon; Eunju Jeon; Daesik Kim — Genome medicine 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a general-purpose AI-designed high-fidelity nuclease and prime editor platform (OpenCRISPR-1/PE7) with eVLP delivery, which is technically relevant to future correction of a heterozygous missense variant like SAMHD1 A565T but has no direct disease-specific content.
DOI: 10.1186/s13073-026-01682-2

A First-in-Human Base Edit Gene Therapy for CD40L Deficiency X-Linked Hyper IgM (XHIGM) Syndrome (from gene therapy / primary immunodeficiency)
S. de Ravin; Tyra Estwick; Yuzhi Yin; Michelle Ma; Siyuan Liu — Journal of Human Immunity 2026
Score: 5/10 | Pathways: gene-therapy-delivery, treatment-target

This describes base editing of autologous HSC/T cells for a monogenic primary immunodeficiency (CD40L/XHIGM), offering a relevant precedent for gene correction strategies in immune cells applicable to a het missense variant like SAMHD1 A565T, though the disease and mechanism are unrelated to interferonopathy/mitochondrial pathways.
DOI: 10.70962/cis2026abstract.1

On-Demand Personalized Gene Editing to Treat IRF4 p.T95A Immunodeficiency (from Gene therapy/immunodeficiency (IEI) translational research)
V. Toskov; Sébastien Levesque; M. Elkins; Haarika Kathi; C. Platt — Journal of Human Immunity 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery, clinical-phenotype

Not SAMHD1-related, but demonstrates allele-specific prime editing correction of a dominant-negative/neomorphic immune transcription factor variant in patient T cells, directly relevant to future gene correction strategies for a het missense variant like SAMHD1 A565T.
DOI: 10.70962/cis2026abstract.17

Restoration of the immune system with base editing and non-genotoxic conditioning in a Rag2 point-mutant mouse model. (from gene therapy / hematopoietic stem cell transplantation)
Carla Dib; Jack A. Queenan; Hana Willner; Leah Swartzrock; Carsten T. Charleswor — Molecular therapy : the journal of the American Society of Gene Therapy 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Demonstrates base editing with eVLPs and non-genotoxic conditioning to correct a point-mutant HSPC immune disorder, directly relevant to future gene-correction strategies for a het missense variant like SAMHD1 A565T but not disease-specific.
DOI: 10.1016/j.ymthe.2026.04.010

Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID (from gene therapy / immunodeficiency genetics)
Ziwen Huang; Zhenxi Cai; Peiyang Yan; Yi-Heng Hu; Ying Wang — Advanced Biotechnology 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

Demonstrates base editing correction of a monogenic immunodeficiency gene (Artemis/SCID) ex vivo, offering a technical template relevant to future correction of het SAMHD1 missense variants like A565T but with no direct SAMHD1 or interferonopathy mechanism.
DOI: 10.1007/s44307-026-00115-w

Efficient prime editing in vivo and in vitro using lipid nanoparticles. (from gene therapy/nanomedicine engineering)
A. Jiang; Ana Cristian; Dominique L. Brooks; Emily R. Feierman; Paul Z. Chen — Nature nanotechnology 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates a generalizable LNP-based prime editing delivery platform for liver correction of point mutations, relevant as a potential future correction strategy for SAMHD1 A565T though not targeting immune/myeloid cells directly.
DOI: 10.1038/s41565-026-02200-6

Optimizing Peptide Ionizable Lipids Enables Efficient and Low‐Toxicity mRNA Delivery for In Vivo Prime Editing and Protein Replacement Therapy (from materials science / gene therapy delivery engineering)
Qiu Wang; Yi Lin; Jiahui Xiao; Keqing Xu; Zijin Luo — Advanced Materials 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Describes a novel LNP platform for in vivo prime editing and mRNA delivery, relevant as a potential future gene correction vehicle for a SAMHD1 missense variant but not tissue/cell-type specific to immune/myeloid cells and lacks any disease-mechanism content.
DOI: 10.1002/adma.202522552

The Improvements and Applications of Prime Editing (from molecular genetics/gene therapy engineering)
Yaoyao Lu; C. Bouchard; Nicolas Soucy; A. Siddika; Gabriel Lamothe — DNA 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing advancements and delivery methods (AAV, LNP, EV) relevant to future correction of heterozygous missense variants like SAMHD1 A565T, though not disease-specific.
DOI: 10.3390/dna6010016

A primer on prime: A prime editing update from advances to first-in-human trial. (from Gene therapy/genome editing)
Caleb Lushington; Paul Thomas; Fatwa Adikusuma — Molecular therapy : the journal of the American Society of Gene Therapy 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

General prime editing review with no SAMHD1 or immune-specific content, but relevant as a technology update for future correction of het missense variants like p.A565T.
DOI: 10.1016/j.ymthe.2026.04.033

Advances in Engineered Virus-Like Particles for Genome Editing and Therapy (from gene therapy/bioengineering)
Se Hyeok Son; S. Woo; Ayeon Choi; S. Ahn; Hee Chan Yoo — Biodrugs 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews eVLP delivery platforms for genome editing (Cas9/base/prime editors), relevant as a potential future correction strategy for a heterozygous missense variant like SAMHD1 A565T but with no disease-specific mechanistic content.
DOI: 10.1007/s40259-026-00767-z

🟢 Low Relevance

Targeting the NLRP3 Inflammasome in Atherosclerosis: A Review of Natural Products and Their Molecular Mechanisms (from Cardiology/vascular pharmacology)
Su-Jin Bae; Hye-Min Seo; Si-Eon You; Junho H. Lee — International Journal of Molecular Sciences 2026
Score: 4/10 | Pathways: NLRP3, NF-kB-NLRP3-priming, mito-ROS-NF-kB

Reviews NLRP3 inflammasome activation (ROS, TLR4/NF-κB priming, mitochondrial ROS, autophagy) in atherosclerosis using natural product inhibitors, sharing core pathway mechanisms but no SAMHD1, interferon, or family-phenotype connection.
DOI: 10.3390/ijms27083650

Sarsasapogenin attenuates renal ischemia-reperfusion injury by inhibiting the NF-κB pathway and NLRP3 inflammasome-mediated pyroptosis. (from Nephrology/pharmacology (natural compound therapeutics))
Q. Yuan; Yaoke Li; Kaiwen Shen; Ruibo Zhang; Qiang Wang — International immunopharmacology 2026
Score: 4/10 | Pathways: NLRP3, NF-kB-IKK

This paper demonstrates NF-κB/NLRP3-mediated pyroptosis in a renal ischemia-reperfusion model, offering generic pathway overlap but no mitochondrial dNTP, cGAS-STING, or SAMHD1-specific mechanism relevant to the syndrome.
DOI: 10.1016/j.intimp.2026.116872

Rational design of a V-shaped DNA-targeted photosensitizer enables endogenous DNA damage-driven cGAS-STING activation and systemic antitumor immunity (from Oncology/biomaterials (photodynamic therapy))
Yi Cai; Cai-Yun Wang; M. Dong; Zhang Lin; Caiqiang Liao — Materials Today Bio 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, other

This is a cancer photodynamic therapy paper using cGAS-STING/NLRP3 pathway activation as a tumor immunotherapy mechanism, sharing pathway components but with an artificial DNA-damage trigger unrelated to SAMHD1 dNTPase dysfunction or mitochondrial nucleotide biology.
DOI: 10.1016/j.mtbio.2026.103290

TRU-PE: A Universal, Trackable Prime Editor Toolkit for Robust Single-and Multi-Locus Genome Engineering (from Genome engineering/synthetic biology)
Zhichao Qiu; Keke Sun; Qingwei Zeng; Ziwei Luo; Xinran Liu — bioRxiv 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a general prime editing toolkit improving delivery/efficiency and multiplexing, with no direct SAMHD1 or immune/myeloid cell application shown, though the underlying technology is relevant to future correction of the p.A565T variant.
DOI: 10.64898/2026.02.20.706938

In vitro and in vivo base editing of CCR5 in hematopoietic stem cells confers HIV-1 resistance. (from Gene therapy/virology)
Anna K. Anderson; Aphrodite Georgakopoulou; A. Kuhlmann; Hongjie Wang; Andrew O. — Molecular therapy : the journal of the American Society of Gene Therapy 2026
Score: 4/10 | Pathways: gene-therapy-delivery

Demonstrates in vivo base editing in HSCs using helper-dependent adenoviral vectors for CCR5/HIV, offering a relevant delivery platform analog for future SAMHD1 correction but with no direct SAMHD1/interferonopathy mechanism.
DOI: 10.1016/j.ymthe.2026.03.018

Epigenome editing of human hematopoietic stem cells enables sustained and reversible thrombosis prevention (from Hematology/gene therapy engineering)
Tianyi Ye; Wanying Xu; Maria N. Barrachina; Peng Lyu; Mateusz Antoszewski — bioRxiv 2026
Score: 4/10 | Pathways: gene-therapy-delivery

This paper demonstrates HSC epigenome editing for durable gene silencing (ITGB3) relevant as a delivery/technology platform for future SAMHD1 correction strategies but has no direct connection to SAMHD1 or the interferon-mitochondrial-inflammasome mechanism.
DOI: 10.64898/2026.03.27.714536

O14 Next-generation sequencing precision: on- and off-target analysis of gene editing in recessive dystrophic epidermolysis bullosa (from Dermatology/gene therapy)
A. Kazemizadeh; I. Brooks; Carina Graham; Yara Alrokh; I. Guri — British Journal of Dermatology 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates base/prime editing correction of a COL7A1 nonsense variant with off-target NGS/WGS analysis, offering a methodological analog for correcting a heterozygous missense variant like SAMHD1 A565T but is unrelated to the disease's interferon-mitochondrial pathways or cell types (fibroblasts/keratinocytes vs. myeloid/immune cells).
DOI: 10.1093/bjd/ljaf429.014

Engineering precision oncology: Targeting tumors and immune cells with lentiviral vectors (from gene therapy vector engineering / oncology)
J. Rossi; Chiara Martinello; Riccardo G. Sorrentino; V. Guyonnet-Duperat; S. Ami — Molecular Therapy Oncology 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

This is a general lentiviral/VLP engineering review for oncology delivery with only tangential mention of prime-editing VLPs and no direct connection to SAMHD1 biology or the interferon-mitochondrial mechanism.
DOI: 10.1016/j.omton.2026.201197

Synonymous editing alters ion channel function, favoring prime editing for retinal disease correction (from Ophthalmology/retinal genetics)
Meha Kabra; M. Moosajee; Ana Navarrete; Gregory A. Newby; Piper A Rawding — International Journal of Biological Sciences 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

Demonstrates prime editing's superiority over base editing for precise missense correction with functional validation, methodologically relevant to future SAMHD1 A565T correction strategies but unrelated to disease mechanism or affected tissue.
DOI: 10.7150/ijbs.132743

In vivo base editing alleviates hepatic iron accumulation and fibrosis in models of HFE-related hereditary hemochromatosis. (from Hepatology/gene therapy)
Vanessa Hamann; Sebastian Hook; P. Sujariyakul; Rajesvaran Ramalingam; M. Sgodda — Journal of hepatology 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

This paper demonstrates LNP-delivered base editing for HFE hemochromatosis in hepatocytes, technically relevant as a gene correction delivery platform but not targeting immune/myeloid cells or SAMHD1-related pathways.
DOI: 10.1016/j.jhep.2026.05.022

In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder (from Hepatology/Metabolic genetics (peroxisomal disorder gene therapy))
Xin D. Gao; Maximiliano Presa; Jordyn E Duby; Jennifer Ryan; Pierre-Alexandre Pi — Nature biomedical engineering 2026
Score: 4/10 | Pathways: gene-therapy-delivery

This paper demonstrates in vivo adenine base editing via AAV9/LNP delivery to correct a liver-specific monogenic disease, offering a relevant gene-correction technology template but no direct connection to SAMHD1, interferon/inflammasome pathways, or mitochondrial dNTP mechanisms.
DOI: 10.1038/s41551-026-01651-5

The next generation of lipid nanoparticles for in vivo engineering and targeted delivery (from nanomedicine/drug delivery engineering)
Penghui Zhao; Zerui Zhou; Jie Chen; Wei Sun; Zhen Tian — Nano Research 2026
Score: 4/10 | Pathways: gene-therapy-delivery

This is a general review of next-generation LNP delivery technology relevant to gene/mRNA therapeutics but does not address SAMHD1, its mechanistic pathways, or myeloid/immune-specific editing applications directly.
DOI: 10.26599/nr.2026.94908949

Prime Editing Exhibits Limited Genome-Wide Off-Target Effects in Cellular and Embryonic Gene Editing (from genome editing / molecular biology)
Jitan Zheng; Mingdi Wu; Xueyan Wang; Zhenrui Zuo; Chikai Zhou — Cells 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General prime editing off-target safety benchmarking (PE5max vs PE3max) is a background gene-therapy platform advance not specific to SAMHD1 correction or myeloid/immune cell delivery.
DOI: 10.3390/cells15050438

Prime editing in neuropsychiatric disorders: From mutation‐specific target selection to clinical translation (from Neurology/gene therapy engineering)
Tianshan Ji; Yuan Zhang; Jinyi Zhao; Yi Lu; Chengkun Wang — Neuroprotection 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

Discusses general prime editing technology and delivery advances for neuropsychiatric disorders but is not specific to SAMHD1, myeloid/immune cell editing, or immune pathway mechanisms relevant to the disease profile.
DOI: 10.1002/nep3.70041

Optimizing prime editing: Advances in efficiency enhancement. (from molecular genome engineering/biotechnology)
Ying Qu; Yingying Li; Tong Shao; Jingyu Kuang; Yanhua Qi — Biotechnology advances 2026
Score: 4/10 | Pathways: prime-editing

This is a general technical review of prime editing efficiency optimization with no immune/myeloid cell context or connection to SAMHD1 correction strategies specifically, though relevant as background technology for future gene correction of the A565T variant.
DOI: 10.1016/j.biotechadv.2026.108815

Building CRISPR-Based Gene-Editing Platforms for Personalized Medicine: The Next Step in Interventional Genetics (from gene therapy/genetic engineering)
Sebastian Hernandez Rodriguez; Toshifumi Yokota — Genes 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

A general review of CRISPR base/prime editing platforms for personalized medicine, relevant only as background to potential future correction of the SAMHD1 A565T variant but with no disease-specific or pathway-specific content.
DOI: 10.3390/genes17060631

P19 Proof of concept for a variant-agnostic, permanent DNA editing cure for dystrophic epidermolysis bullosa (from Dermatology / gene therapy technology development)
Carina Graham; Stephen L Hart; John McGrath; Joanna Jacków-Malinowksa — British Journal of Dermatology 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates prime editing/eePASSIGE and LNP delivery technology relevant to future gene correction strategies but targets COL7A1/skin disease rather than SAMHD1 or immune/myeloid cells specifically.
DOI: 10.1093/bjd/ljaf429.046

Gene-Editing and Drug Delivery Convergence: Pharmaceutical Strategies for Precision Gene Therapy (from Pharmaceutical sciences/drug delivery)
Sanjeev Kumar; K. Raj; Kirti Rani; M. Kumawat; Priya Srivastava — Journal of Pharmacology, Genetics and Molecular Biology 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

General review of gene-editing delivery platforms with no SAMHD1, interferon, or mitochondrial mechanism specificity, though broadly relevant to future correction of the A565T variant.
DOI: 10.64062/jpgmb.vol2.issue2.1

Copper oxide nanoparticles induce size dependent endothelial damage and cuproptosis via MAPK/NF-κB/NLRP3 signaling pathway. (from Toxicology/nanomaterial safety science)
Ye Cheng; Xiangyu Cao; Dawo Liu — Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2026
Score: 3/10 | Pathways: NLRP3, mito-ROS-NF-kB

This is a nanotoxicology study on copper oxide nanoparticles inducing endothelial cuproptosis via MAPK/NF-κB/NLRP3, sharing pathway components but with no connection to SAMHD1, interferon signaling, or mitochondrial dNTP biology.
DOI: 10.1016/j.fct.2026.116171

Recalibrating cell fate: targeting the mitochondrial signaling hub with natural active compounds to inhibit regulated cell death in diabetic kidney disease (from Nephrology/diabetes)
Yinzhong Dai; Chenguang Wu; Jiaying Zheng; Keqin Zhao; Shimei Hua — Frontiers in Physiology 2026
Score: 3/10 | Pathways: NLRP3, other

This paper discusses mitochondrial-driven NLRP3/apoptosis/ferroptosis crosstalk in diabetic kidney disease with natural compounds, sharing conceptual overlap with mitochondrial-NLRP3 signaling but no connection to SAMHD1, interferon pathways, or the specific disease mechanism.
DOI: 10.3389/fphys.2026.1774714

ASS1 Promotes Atherosclerotic Inflammation Through the NLRP3/IL-33/ST2 Axis in Ox-LDL-Induced Foam Cells. (from Cardiology/vascular biology)
Shaoyu Wu; Feihuang Han; Z. Qiao; S. Yuan; Xiaohui Bian — Frontiers in bioscience 2026
Score: 3/10 | Pathways: NLRP3, other

Describes NLRP3 inflammasome activation via STAT3/IL-33/ST2 in atherosclerotic foam cells, an unrelated ASS1-driven mechanism with only superficial NLRP3 overlap to the SAMHD1 syndrome's interferon-mitochondrial axis.
DOI: 10.31083/fbl47686

A bioadhesive antioxidant dual-crosslinked hydrogel mitigates endothelial pyroptosis to enhance ischemic flap survival. (from Plastic/reconstructive surgery, biomaterials engineering)
Kai Yang; Pei Zou; Yikun Ju; Shuai Zhu; Hongli Zhao — Journal of nanobiotechnology 2026
Score: 3/10 | Pathways: NLRP3, other

This paper discusses NLRP3 inflammasome suppression and endothelial pyroptosis in an unrelated surgical/tissue engineering context (flap survival), not connected to SAMHD1 mechanism or interferonopathy.
DOI: 10.1186/s12951-026-04767-7

Advances in lipid nanoparticles delivering genetic medicines for solid cancers (from oncology drug delivery)
Fan Yang; Tristan A. Scott — Molecular Therapy. Nucleic Acids 2026
Score: 3/10 | Pathways: gene-therapy-delivery

General review of LNP delivery for solid tumor genetic medicines, oncology-focused rather than immune/myeloid cell targeting relevant to SAMHD1 correction strategies.
DOI: 10.1016/j.omtn.2026.102838

Teknologi Pengeditan Gen pada Anemia Sel Sabit (Sickle Cell Disease) : CRISPR-Cas9, Base Editing, dan Prime Editing (from Hematology/genetic engineering education)
N. Fadhilah; H. Hartati — Biocaster : Jurnal Kajian Biologi 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

Reviews CRISPR/base/prime editing for sickle cell disease (HBB gene) with no connection to SAMHD1, interferon, or NLRP3 pathways, though it touches gene-editing platforms of tangential technical relevance to future SAMHD1 correction strategies.
DOI: 10.36312/biocaster.v6i1.861

Induced Pluripotent Stem Cells and Gene Editing: A Transformative Era in Regenerative Medicine (from regenerative medicine/stem cell biology)
Sujitha Mathivanan; Balaji A; Syed Mohamed Omar S; H. Babu; Sujan S — International Journal of Drug Delivery Technology 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General review of iPSC and gene-editing (CRISPR/base/prime editing) technology platforms with no specific connection to SAMHD1, interferonopathy, or mitochondrial-inflammasome pathways beyond generic mention of prime editors.
DOI: 10.25258/ijddt.16.5.136

Gene Editing Strategies for Neurological and Mental Disorders: Advances in Delivery, Methodology, and Clinical Translation (from Neurology/gene therapy delivery)
A. Elias; S. Stern — Cells 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a broad review of CNS-focused gene editing delivery and clinical milestones with no direct connection to SAMHD1, mitochondrial-interferon pathways, or NLRP3/cGAS-STING mechanisms, though prime/base editing methodology has tangential future relevance to correcting SAMHD1 variants.
DOI: 10.3390/cells15080720

Inflammasome-Primed Neutrophils Aggravate Atherosclerosis in Cigarette Smoking. (from Cardiology/vascular biology)
Dipanjan Chattopadhyay; Nitin Nitin; Robert M. Jaggers; Baskaran Athmanathan; Kr — Circulation research 2026
Score: 3/10 | Pathways: NLRP3, mito-ROS-NF-kB

Describes neutrophil-driven NLRP3/IL-1beta inflammation in atherosclerosis via S100A8/A9, tangentially touching NLRP3 biology but with no SAMHD1, interferon, or mitochondrial dNTP pathway involvement.
DOI: 10.1161/CIRCRESAHA.125.327714

Lipid nanoparticle-based non-viral in situ gene editing of congenital ichthyosis-causing mutations in human skin models. (from Dermatology/gene therapy)
Dilem C Apaydin; Gaurav Sadhnani; Tiffany Carlaw; Jan Renziehausen; Elena Lizuno — Cell stem cell 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes LNP-delivered base editing for a skin-specific TGM1 splice mutation unrelated to SAMHD1 pathways, but shares generic gene-correction/LNP delivery methodology of tangential relevance to future SAMHD1 correction strategies.
DOI: 10.1016/j.stem.2026.01.001

A clinically relevant retrograde intraductal injection (RIDI) for lipid nanoparticles-mediated base editing in the pancreas. (from Gastroenterology/pancreatology gene therapy delivery engineering)
Deepak Sahel; Amita Tiyaboonchai; L. Wakefield; Jonas Renner; A. Jozić — Nanomedicine : nanotechnology, biology, and medicine 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes LNP-based base editing delivery to pancreatic acinar cells via a novel injection route, which is tangential gene-editing-delivery technology but not targeted to immune/myeloid cells or SAMHD1-relevant tissue.
DOI: 10.1016/j.nano.2026.102933

Amplified genome editing by in vivo editor production (from genetic engineering/synthetic biology)
Wayne Ngo; Daniel Rosas-Rivera; Kevin M. Wasko; Longhui Qiu; Min Hyung Kang — bioRxiv 2026
Score: 3/10 | Pathways: gene-therapy-delivery

Describes a generic in vivo genome editing delivery amplification technique (NANITE) in liver, not targeting SAMHD1 or immune/myeloid cells, but tangentially relevant as a gene-therapy delivery advance.
DOI: 10.64898/2026.01.13.699115

Nanoparticle-mediated mRNA delivery for cancer, autoimmunity, and genetic diseases: a rapid review (from pharmaceutical/drug delivery science)
Ugwu Okechukwu Paul-Chima; F. C. Ogenyi; Mariam Basajja; C. N. Ugwu; M. Mustafa — Frontiers in Drug Delivery 2026
Score: 3/10 | Pathways: gene-therapy-delivery

General review of LNP/mRNA delivery for cancer, autoimmunity, and genetic disease with no direct connection to SAMHD1, interferon-mitochondrial mechanism, or family phenotypes beyond generic gene-therapy delivery relevance.
DOI: 10.3389/fddev.2026.1793322

Programmable lipid nanoparticles for RNA therapeutics: Design principles and clinical translation (from pharmaceutical sciences/nanomedicine)
Mahdi Navid Talemi; Marzieh Ramezani Farani; Naiyereh Alipour Eskandani; Danial * — Materials Today Bio 2026
Score: 3/10* | Pathways: gene-therapy-delivery

General LNP design review for RNA/gene therapeutics with no SAMHD1, interferonopathy, or mitochondrial pathway content, only tangentially relevant as a potential future delivery platform for immune/myeloid gene correction.
DOI: 10.1016/j.mtbio.2026.102774

Rewriting hepatic fate: emerging gene therapy strategies for liver disease (from Hepatology/gene therapy)
Ralf Weiskirchen — Journal of Translational Genetics and Genomics 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General review of liver-directed gene therapy platforms (AAV, LNP, prime/base editing) with no SAMHD1, interferonopathy, or immune-cell delivery focus, only tangentially relevant via generic gene-correction technology overlap.
DOI: 10.20517/jtgg.2026.36

Optimized lipid nanoparticles for pulmonary delivery of CRISPR/Cas9 targeting KRAS G12S in lung cancer. (from Oncology/pulmonary gene therapy)
Moritz Marschhofer; Siyu Chen; Müge Molbay; Benjamin Winkeljann; Ersilia Villano — Journal of controlled release : official journal of the Controlled Release Society 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes LNP-CRISPR delivery for KRAS-mutant lung cancer, a general gene-editing delivery technology unrelated to SAMHD1 mechanisms, immune cells, or interferonopathy pathways, though tangentially relevant as a gene-editing delivery platform.
DOI: 10.1016/j.jconrel.2026.114607

A Rapidly Excretable, ROS-Scavenging Ionizable Lipid Decouples mRNA Delivery Potency from Toxicity (from biomedical engineering/ophthalmology (LNP drug delivery, retinal gene therapy))
Yeji Lee; H. Jeong; Eunbin Kim; Yuna Hwang; Yongjoo Byeon — bioRxiv 2026
Score: 3/10 | Pathways: gene-therapy-delivery, other

This paper describes a novel ionizable lipid nanoparticle for mRNA/gene editing delivery with improved safety, which is only tangentially relevant as a general delivery platform technology rather than addressing SAMHD1 mechanisms or immune cell/myeloid targeting specifically.
DOI: 10.64898/2026.04.07.716828

CRISPR-Cas9 Applications in Gene Therapy: Advances, Challenges, and Future Perspectives (from Gene therapy/biomedical engineering)
Imran khan Yousafzai; Aqsa Mehreen; Nadia Noreen; Khadija Tariq; Akram ul Haq — Advances in Modern Biomedicine 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR-Cas9 review covering unrelated single-gene disorders with only generic mention of prime/base editing and delivery, lacking specific application to SAMHD1 or immune/myeloid cell correction relevant to this family's variant.
DOI: 10.64229/4r4mbv88

Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges (from bioengineering/nanomedicine)
Eunhye Cho; Je-Heon Lee; Jiyu Kim; Jaewon Choi; Mikyung Kang — Journal of Biological Engineering 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This is a general review of EV-based CRISPR delivery/diagnostics with no mention of SAMHD1, interferon-mitochondrial pathways, or myeloid/immune-specific gene correction relevant to the A565T variant.
DOI: 10.1186/s13036-026-00673-6

Engineering delivery platforms for CRISPR-Cas and their applications in healthcare, agriculture and beyond (from nanotechnology/bioengineering)
Nisha Bharti; Unnati Modi; Dhiraj Bhatia; Raghu Solanki — Nanoscale Advances 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General review of CRISPR/base/prime editor delivery platforms with no SAMHD1, immune cell, or myeloid-specific focus, offering only broad background relevance to future gene correction strategies.
DOI: 10.1039/d5na00535c

Abstract LB155: Durable anti-tumor immunity through in vivo CAR T cell engineering using the RetroT all-RNA genome integration platform (from oncology/cell therapy engineering)
Jian Ding; Meghan Harris; Edward Cochran; Thach Ty; Glenn Leary — Cancer Research 2026
Score: 3/10 | Pathways: gene-therapy-delivery

Describes an in vivo CAR T RNA-based genome integration platform for oncology unrelated to SAMHD1 mechanism, though RNA delivery tech could theoretically inform future gene correction strategies for immune cells.
DOI: 10.1158/1538-7445.am2026-lb155

Polypeptide nanoparticles: a clinically validated, versatile delivery platform for RNA therapeutics (from pharmaceutical sciences/nanotechnology)
F. Poon; Weixiong Zhong; Weiwei Tian — Nucleic Acid Insights 2026
Score: 3/10 | Pathways: gene-therapy-delivery

Discusses a non-viral RNA delivery platform (PNP) broadly applicable to siRNA/mRNA therapeutics but lacks any specific connection to SAMHD1, immune cell/myeloid targeting, or the interferon-mitochondrial-NLRP3 mechanistic axis central to this disease profile.
DOI: 10.18609/nai.2026.032

Gene-based Therapies for Genetic Cardiomyopathies: Molecular Medicine for Heart Disease. (from Cardiology)
Shubham Sharma; C. Sadasivan; Yang Yan; G. Oudit — The Canadian journal of cardiology 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

This is a general review of gene-based therapies for cardiomyopathies (AAV vectors, base/prime editing, ASOs) with no SAMHD1 relevance and no myeloid/immune cell delivery focus, only tangentially connected via generic gene-editing technology.
DOI: 10.1016/j.cjca.2026.01.055

From mechanism to medicine: CRISPR‒Cas9 delivery strategies, therapeutic applications and translation challenges (from nanotechnology/gene therapy engineering)
Shivani Makhijani; Glowi A Alasiri; M. S. Quadri; Rahul G. Ingle — Discover Nano 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR delivery/therapeutic review with no SAMHD1-specific or pathway-specific content, only tangentially relevant as background for future gene correction strategies.
DOI: 10.1186/s11671-026-04653-z

Prime editing for ocular gene therapy and disease modeling: a narrative review of advances, delivery, and translational readiness. (from Ophthalmology)
Qing Zhang; Yanhui Yang; Xionggao Huang; Junkai Ma; Yajian Duan — Experimental eye research 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews prime editing technology and delivery advances generically for ocular disease but has no direct connection to SAMHD1 correction, immune/myeloid delivery, or the interferon-mitochondrial mechanism.
DOI: 10.1016/j.exer.2026.110891

Gene Editing Therapies Targeting Lipid Metabolism for Cardiovascular Disease: Tools, Delivery Strategies, and Clinical Progress (from Cardiology/lipid metabolism gene therapy)
Zhuoying Ren; Junsheng Zhou; Dongshan Yang; Yanhong Guo; Jifeng Zhang — Cells 2026
Score: 3/10 | Pathways: gene-therapy-delivery

Reviews gene editing delivery tools (AAV, LNP, VLP, base/prime editors) for liver-targeted lipid genes in cardiovascular disease, providing general technology overlap but no direct connection to SAMHD1, interferonopathy, or myeloid/immune cell editing.
DOI: 10.3390/cells15020134

Gene Editing Strategies (CRISPR) for Inherited Cardiomyopathies: Ethical, Technical and Clinical Review (from Cardiology / gene therapy bioethics)
Pavithra Amritkumar; Jayannan; Prabhavathi Devi N; K. M; P. S — International Journal of Drug Delivery Technology 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

A general review of CRISPR/base/prime editing for cardiomyopathy genes (MYH7, MYBPC3, LMNA, PKP2) with no SAMHD1, interferon, or mitochondrial-innate-immune pathway relevance, only tangential technical overlap in editing/delivery platforms.
DOI: 10.25258/ijddt.16.10s.22

Coordinated regulation using small-molecule drugs enables controlled therapeutic genome editing and enhanced genomic precision in situ. (from Synthetic biology/genome editing engineering)
Ju Zhang; Li Chen; Xingyu Zhu; Yushan Cai; Shixian Wei — Science translational medicine 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a general-purpose inducible genome editing control system (PRINCE/Little Prince) applied to hypercholesterolemia and AMD, with no connection to SAMHD1, immune/myeloid targeting, or the interferon-mitochondrial pathways central to this disease profile.
DOI: 10.1126/scitranslmed.adx7857

CRISPR-Cas Systems: From Bacterial BiochemistrytoBiomedical Revolution—A Review of Mechanisms, Delivery Challenges, and Therapeutic Gene Editing (from molecular biotechnology/genome editing)
N. Bhojak; S. Nayak; S. Acharya — IFR Journal of Biochemistry and Biomedical Science 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR/prime editing review with no SAMHD1, mitochondrial, or interferonopathy-specific content, only tangentially relevant as background for future gene correction strategies.
DOI: 10.70146/bbsv02i01.003

CRISPR-Cas9-Mediated Gene Editing in Hematological Disorders: Advancing Translational and Clinical Applications (from Hematology/gene therapy)
Abhay Singh; Rishikesh Kumar; P. Chauhan; M. Mallikarjuna; Ravi Thaker — Cureus 2026
Score: 3/10 | Pathways: gene-therapy-delivery

General narrative review of CRISPR-Cas9 in hematological disorders (hemoglobinopathies, CAR-T) with no direct SAMHD1, interferonopathy, or mitochondrial nucleotide mechanism relevance beyond generic HSC/immune cell editing platform discussion.
DOI: 10.7759/cureus.108691

CRISPR–Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges (from neurology/gene therapy)
Raya Kh. Yashooa; A. Nabi; S. Smail; Sarkar Sardar Azeez; Wissam Albeer Nooh — Frontiers in Neurology 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general CRISPR/prime-editing review focused on neurodegenerative disorders (AD/PD/HD/ALS) with no mention of SAMHD1, interferon signaling, or mitochondrial-inflammasome pathways, though it touches broadly on gene-editing delivery challenges relevant to future SAMHD1 correction strategies.
DOI: 10.3389/fneur.2025.1737468

CRISPR–Cas Systems in Human Disease Therapy: Advances, Clinical Applications, Limitations, and Future Directions (from Gene therapy/genome engineering)
Gedion Mengistu — The Journal of Gene Medicine 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General CRISPR/prime-editing review without mention of SAMHD1, myeloid/immune cell targeting, or any disease pathway relevant to this syndrome, offering only generic background on gene correction technology.
DOI: 10.1002/jgm.70091

Nanoengineering Systems for Gene Therapy: Mechanisms, Modalities, and Future Directions (from nanotechnology/bioengineering)
Raheem Mais; Ayush Kumar; Armand Ahmetaj; Gaby Burgos-Crespo; M. Sanchez — International Journal of Molecular Sciences 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General review of nanomaterial delivery for CRISPR/base/prime editing without SAMHD1, immune-cell/myeloid focus, or disease-specific mechanism, offering only background relevance to future gene correction strategies.
DOI: 10.3390/ijms27135988

CRISPR-Based Therapeutics: Molecular Mechanisms of Gene-Targeted Drug Action (from Genome engineering / biotechnology)
Kaan Karakas — Next Frontier For Life Sciences and AI 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General review of CRISPR/base/prime editing mechanisms without specific application to SAMHD1 or immune/myeloid cell correction, offering only tangential background relevance.
DOI: 10.62802/d0cp8g33

↩ Re-run 14:21 UTC | Model: claude-sonnet-5

Summary: 16 new papers | 3 high-relevance (≥7) | 10 medium (5–6) | 3 low (3–4)

🔴 High Relevance

C107-14 Exploring How Mitochondrial Damage and Dysfunction Influences Tlr9 and Cgas-sting Pathways in Obesity and Influenza (from Pulmonology/Critical Care Medicine (ARDS, influenza))
A. Kumar; J. Silva; X. Li; D. Al Dikka; K. Epler — American Journal of Respiratory and Critical Care Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-NLRP3-priming, mito-ROS-NF-kB, clinical-phenotype

This paper demonstrates mtDNA release triggering competing cGAS-STING (IFN-I) versus TLR9 (inflammatory) pathways in obesity/viral infection, directly paralleling the BLUE loop mtDNA-sensing mechanism and post-viral inflammatory phenotype central to the SAMHD1 syndrome, though without any SAMHD1 or genetic component.
DOI: 10.1093/ajrccm/aamag162.233

From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation. (from Neurology/Neurodegeneration)
Ghaleb A. Oriquat; A. Abdulqader; Hamrayev Farid; Z. Ashurov; Abduvali Sottarov — Brain research bulletin 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target, other

This review details the core cGAS-STING pathway (Loop A) driving sterile neuroinflammation via mitochondrial DNA release and PINK1-Parkin-mitophagy crosstalk, mechanistically relevant to the neurological/AuDHD phenotypes and interferonopathy axis in the SAMHD1 family, though it lacks direct SAMHD1 or NLRP3/dNTP linkage.
DOI: 10.1016/j.brainresbull.2026.111963

Multiple Roles of G3BP1 in Regulating STING-Dependent Interferon and Cytokine Induction by Cytosolic dsDNA and HSV-1 Infection (from virology/molecular cell biology)
Trupti Devale; Praveen Manivannan; K. Malathi — Viruses 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target

Details G3BP1 as a novel regulator of cGAS-STING DNA sensing and STING trafficking, directly relevant to the BLUE loop (cGAS/STING/IFN-I) central to the disease mechanism, though it does not involve SAMHD1 directly.
DOI: 10.3390/v18070719

🟡 Medium Relevance

Hypoxia-Inducible Factor Prolyl Hydroxylase EGLN3 Stabilizes Atherosclerotic Plaques in ApoE-/- Mice Independently of Its Catalytic Activity. (from cardiovascular biology/atherosclerosis)
Jin Ying; Xu Lei; Xiong Yulian; Sun Dejiao; Liu Lanlan — Arteriosclerosis, thrombosis, and vascular biology 2026
Score: 6/10 | Pathways: NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

This paper demonstrates mitochondrial ROS/mtDNA release driving NLRP3 inflammasome activation via TRAF6-NFκB crosstalk in macrophages, closely mirroring the disease's mito-ROS-NFκB and NLRP3 priming axes, though it is set in atherosclerosis rather than SAMHD1-related interferonopathy.
DOI: 10.1161/ATVBAHA.125.323765

The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. (from Neurology/Parkinson's disease and gut-brain axis research)
Ahmed M. Abdelaziz — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

This paper details a cGAS-STING-driven neuroinflammatory feed-forward loop involving mtDNA DAMPs and IFN signaling, directly relevant to the interferon-mitochondrial axis in the SAMHD1 syndrome, though it addresses Parkinson's disease and gut-brain/glymphatic mechanisms rather than SAMHD1 itself.
DOI: 10.1016/j.intimp.2026.116628

Mechanistic insights and therapeutic potential of targeting the cGAS–STING pathway in neurodegenerative diseases (from Neurology/neurodegeneration)
Huilin Liu; Chun Hu; Hongdou Liu; Ziqing Gong; Shilong Jiang — Journal of Neuroinflammation 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Provides deep mechanistic review of cGAS-STING signaling and mitochondrial DNA-stress-driven neuroinflammation relevant to the BLUE loop and AuDHD/neurologic phenotype, though not SAMHD1-specific.
DOI: 10.1186/s12974-026-03815-1

Emerging Role of the cGAS–STING Signaling Pathway in Multiple Inflammatory Skin Diseases (from Dermatology)
Shasha Zhao; H. Bai; Ying Wang; Yan Yan — Dermatologic Therapy 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

Reviews cGAS-STING pathway dysregulation driving inflammatory skin diseases and therapeutic agonist/inhibitor strategies, directly relevant to Loop A/BLUE mechanism and offering treatment insights applicable to the interferonopathy but without SAMHD1-specific data.
DOI: 10.1155/dth/3322507

Mitochondrial DNA-driven intercellular communication networks in post-infarction ventricular remodeling: the three-threshold model of cGAS-STING activation (from Cardiology (post-infarction remodeling))
Chao Meng; Xiao Xia; Yiying Liu; Jun Li; Shiyi Tao — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, treatment-target

Details mtDNA release/cGAS-STING activation as intercellular DAMP signaling driving cardiac fibrosis/inflammation, mechanistically parallel to the BLUE loop (VDAC1-mtDNA-cGAS-STING) though in a cardiac rather than SAMHD1 context.
DOI: 10.3389/fimmu.2026.1852079

The inflammatory clock: how cGAS-STING ticks in the aging ovary (from Reproductive endocrinology/gynecology)
Yanjing Ma; Yu Chen; Xiong Yuan; Tingyue Li; Hao Luo — Frontiers in Cell and Developmental Biology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype, other

Reviews cGAS-STING as driver of mitochondrial/DNA-damage-induced sterile inflammation, senescence and fibrosis in ovarian aging, directly relevant to the core Loop A mechanism and offers therapeutic parallels (STING inhibitors) though not linked to SAMHD1 or the family's reproductive phenotypes.
DOI: 10.3389/fcell.2026.1771546

Stroke in persistent chronic kidney disease condition alters innate-immunity to escalate mitochondrial dysfunction and aging. (from Nephrology/Neurology (stroke-CKD comorbidity))
Aishika Datta; Karan Sehgal; Deepaneeta Sarmah; Smreeti Dhiman; Birva Shah — npj aging 2026
Score: 6/10 | Pathways: cGAS-STING, other

Demonstrates cGAS-STING-driven mitochondrial dysfunction and accelerated mitochondrial aging in a CKD-stroke model, paralleling the core IFN-mitochondrial mechanism though in an unrelated disease context without SAMHD1 involvement.
DOI: 10.1038/s41514-026-00361-1

Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome. (from Cell biology/ion channel physiology)
C. Magawa; N. Eaton-Fitch; Katsuhiko Muraki; Sonya Marshall-Gradisnik — BMC immunology 2026
Score: 6/10 | Pathways: ME-CFS, other

Investigates mitochondrial Ca2+ dysregulation via TRPM3 in NK cells from ME/CFS patients, directly relevant to the proband's ME/CFS phenotype and mitochondrial dysfunction theme though not through the SAMHD1/interferon-NLRP3 mechanism.
DOI: 10.1186/s12865-026-00849-1

Mitochondrial STING Governs Glycolytic Reprogramming in Diabetic Cardiomyopathy. (from Cardiology/metabolic disease)
Shiwu Zhang; Dechao Zhao; Mengyi Wang; Xiaorong Shen; Fan Yang — Circulation research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates mitochondrial cGAS-STING activation via mtDNA leakage driving metabolic/mitochondrial dysfunction in cardiomyopathy, mechanistically parallel to the BLUE loop and relevant to cardiac phenotype in this interferonopathy family though not disease-specific.
DOI: 10.1161/CIRCRESAHA.125.327867

Context-dependent rewiring of the cGAS-STING pathway in cancer: Implications for immunotherapy and therapeutic resistance. (from Oncology/tumor immunology)
S. Majaz; Ashfaq Ahmad; Dongsheng Liu; A. Ud-Din; Ikramullah Khan — Critical reviews in oncology/hematology 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target

Reviews cGAS-STING pathway biology and therapeutic modulation relevant to the BLUE/Loop A axis but focused on cancer immunotherapy context rather than SAMHD1-driven interferonopathy or mitochondrial dysfunction.
DOI: 10.1016/j.critrevonc.2026.105368

🟢 Low Relevance

Fatty Acid Synthase associates with nuclear-derived cytoplasmic dsRNA molecules and influences antiviral innate immune response (from molecular virology/lipid metabolism)
Charline Pasquier; Mélanie Messmer; Lise Moroge; Lisanne I Knol; Johana Chicher — bioRxiv 2026
Score: 4/10 | Pathways: cGAS-STING, other

Explores FASN-mediated regulation of endogenous cytoplasmic dsRNA and ISG/IFN response near mitochondria, tangentially related to the interferon-mitochondrial axis but not involving SAMHD1, cGAS-STING core mechanism, or NLRP3 directly.
DOI: 10.1101/2025.07.16.662511

Potentiated Tumor Photo-immunotherapy Based on Glutamine Starvation and Interferon Stimulatory DNA-Activated cGAS-STING Pathway. (from Oncology/nanomedicine (photo-immunotherapy))
Jinwen Zhu; Zhenzhen Guo; Renpeng Xia; Peng Miao — ACS medicinal chemistry letters 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This paper uses cGAS-STING activation (via exogenous ISD, not SAMHD1-driven mtDNA leakage) purely as a tumor immunotherapy strategy, sharing pathway terminology but no mechanistic or clinical link to SAMHD1 haploinsufficiency or the family phenotype.
DOI: 10.1021/acsmedchemlett.6c00074

Implementing Photodynamic Therapy to Activate the IFN-1 Pathway in Melanoma Cells: A Protocol for Inducing Immunogenic Cell Death and Enhancing Dendritic Cell Maturation. (from Oncology/Photodynamic therapy immunotherapy)
Fátima María Mentucci; Agustina Ercole; N. B. Rumie Vittar; M. Lamberti — Methods in molecular biology 2026
Score: 3/10 | Pathways: cGAS-STING, other

Describes PDT-induced cGAS/IFN-1/ISG activation in melanoma as an immunotherapy tool, sharing pathway components but unrelated to SAMHD1 mechanism or family phenotype context.
DOI: 10.1007/978-1-0716-4734-9_9

July 9, 2026
in Paper Spotlight
2 min read

From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation

The finding

This is a review article, not a primary research study — it synthesizes existing literature on how chronic cGAS-STING activation, driven by cytosolic self-DNA (genomic instability, mitochondrial dysfunction, retrotransposons), converts a normally protective innate-immune pathway into a driver of neuroinflammation across ALS/FTD, Alzheimer's, Parkinson's, and Huntington's disease. It maps cell-type-specific consequences in microglia, astrocytes, and neurons, and evaluates emerging cGAS-STING-targeted therapeutics. Notably, the authors also flag a retracted PINK1-Parkin-STING report, urging caution about overinterpreting that specific mechanistic link.

Where it fits

This review speaks most directly to ARM 1 (interferon/JAK-STAT), since cGAS-STING sensing of cytosolic DNA and downstream IRF3/7-driven type I IFN is a core upstream input to the tonic IFN signature hypothesized in SAMHD1 A565T carriers. It's also relevant background for ARM 2 (mitochondrial), given its emphasis on mtDNA as an immunogenic trigger and its discussion of PINK1/Parkin-mediated mitophagy — mechanistically adjacent to the ISG15-BECN1 mitophagy block proposed in the SAMHD1 model, though not the same molecule or pathway. For a variant hypothesized to cause chronic, moderate (rather than acute, high) IFN tone, a synthesis of how sustained cGAS-STING signaling reshapes glial and neuronal phenotypes over time is useful context for thinking about potential CNS consequences of chronic SAMHD1-driven interferon exposure — this is conceptual scaffolding, not evidence about SAMHD1 itself.

Caveats

This is a narrative review, not new experimental data; it contains no findings specific to SAMHD1, ANKIB1, or VDAC1, and nothing here should be read as evidence about the A565T variant.
The disease contexts discussed (ALS/FTD, AD, PD, HD) involve largely homozygous/biallelic pathway disruptions or aggregation-driven models in mostly rodent or postmortem human tissue — not the heterozygous, partial-loss-of-function, moderate-tone state relevant to SAMHD1 A565T.
The authors themselves highlight contradictory and retracted data (PINK1-Parkin-STING) within the field, underscoring that mitochondrial-DNA-to-STING mechanisms remain unsettled even in well-studied neurodegeneration models.

What to watch

The open question this raises for the SAMHD1 program is whether the same CNS-specific microglia/astrocyte cGAS-STING amplification loops described here could be operative — at lower, chronic amplitude — in A565T carriers, and whether JAK inhibition (effective in ARM 1) would be sufficient to interrupt such a loop in neural tissue specifically, given the pathway's partly cell-autonomous, partly non-cell-autonomous character in brain.

Source: From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation — 2026.

July 8, 2026
in Weekly Digest, treatment-target, cGAS-STING, NLRP3, gene-editing
30 min read

SAMHD1 Research Digest — 2026-07-08

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 88 papers evaluated | 12 high-relevance (≥7) | 33 medium (5–6) | 43 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Upregulation of macrophage UPP1 promotes lung adenocarcinoma metastasis through an mtROS-cGAS-NLRP3 inflammasome axis. (from Oncology (tumor immunology/lung adenocarcinoma))
Feng MingTao; Gao Chao; Yang YueChao; Li Deheng; Zhou Changshuai — Cell death discovery 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, nucleotide-rewiring, treatment-target

Demonstrates a mechanistically analogous nucleotide-dysregulation → mtROS → mtDNA leakage → cGAS-STING → NLRP3 → IL-1β axis in macrophages driving tumor progression, closely paralleling the PURPLE/BLUE/GOLD SAMHD1 pathways though in an oncology (lung adenocarcinoma) rather than SAMHD1 context.
DOI: 10.1038/s41420-026-03226-4

Melatonin alleviates rheumatoid arthritis via elimination of damaged mitochondria. (from Rheumatology)
Wang Bo; Wu Yanglin; Li Gen; Che Zhenjia; Sun Qi — Autophagy 2026
Score: 7/10 | Pathways: NLRP3, mito-ROS-NF-kB, clinical-phenotype, treatment-target

Demonstrates mitophagy-mediated clearance of damaged mitochondria/mtDNA suppresses NLRP3 inflammasome activation and cytokine release in RA models, directly paralleling the family's mitochondrial-NLRP3 mechanism and RA phenotype seen in the pedigree.
DOI: 10.1080/15548627.2026.2689419

Copper Exposure Promotes Mitochondrial VDAC Oligomerization and Releases mtDNA to Induce Pyroptosis in Pig Hepatocytes. (from Veterinary toxicology/agricultural food chemistry)
Qiu Wenyue; Chen Wei; Yang Shanglong; Xi Hao; Liao Jianzhao — Journal of agricultural and food chemistry 2026
Score: 7/10 | Pathways: VDAC1, NLRP3, treatment-target

Demonstrates the exact VDAC1 oligomerization → mtDNA release → NLRP3 pyroptosis axis (Loop B/BLUE-adjacent) using the same VBIT-4/MCC950 pharmacologic tools referenced in the SAMHD1 mechanism, though in a copper toxicity/veterinary model rather than SAMHD1 context.
DOI: 10.1021/acs.jafc.6c03617

STAT2 R148 variant: A 16th-century founder mutation and clinical response to high-dose JAK inhibitor therapy. (from Clinical genetics/pediatric neuroimmunology)
Parvaneh Nima; Molatefi Rasol; Gruber Conor; Biglari Sajjad; Moradi Leila — Journal of human immunity 2026
Score: 7/10 | Pathways: JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype

STAT2 R148 causes type I interferonopathy via disrupted USP18 negative feedback, directly parallel to the IFN-I overproduction in the SAMHD1 syndrome, and demonstrates JAK inhibitor (ruxolitinib) efficacy as a therapeutic strategy relevant to this family's management.
DOI: 10.70962/jhi.20260001

Design, Synthesis, and Pharmacological Evaluation of cGAS/HDAC Dual Inhibitors for Treatment of Autoimmune Diseases. (from Medicinal chemistry/drug discovery)
Zhou Zihua; Chen Mingjie; Lei Shuyue; Wang Meng; Ding Chunyong — Journal of medicinal chemistry 2026
Score: 7/10 | Pathways: cGAS-STING, AGS-spectrum, treatment-target

A novel small-molecule dual cGAS/HDAC inhibitor with demonstrated efficacy in a murine Aicardi-Goutières syndrome model directly targets the BLUE-loop cGAS-STING pathway central to this SAMHD1 interferonopathy and offers a plausible therapeutic candidate class.
DOI: 10.1021/acs.jmedchem.6c00583

TAX1BP1 targets STING1 via microautophagy and Golgiphagy to limit inflammatory signaling. (from cell biology/autophagy)
Suklabaidya Sujit; Mohanty Suchitra; Harhaj Edward W — Autophagy 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target

Describes a novel negative-feedback mechanism (TAX1BP1-mediated Golgiphagy/microautophagy) that degrades activated STING1, directly relevant to the BLUE pathway's IFN-I amplification and a potential therapeutic node for dampening chronic interferonopathy in SAMHD1 A565T carriers.
DOI: 10.1080/15548627.2026.2658230

Hydroxycinnamic acids target COPII cargo sorting machinery to attenuate inflammation via the cGAS-STING axis. (from Ethnopharmacology/hepatology-metabolic disease)
Ma Xiaojing; Wang Jiaming; Guo Yakun; Nan Yanan; Guo Linyue — Journal of ethnopharmacology 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target, NF-kB-IKK

Demonstrates a druggable choke point (COPII/Sec24-mediated STING trafficking) directly upstream of the cGAS-STING-TBK1-IRF3 axis central to the BLUE/RED interferon loops, with therapeutic implications for metabolic/inflammatory phenotypes relevant to this family's syndrome.
DOI: 10.1016/j.jep.2026.121881

Breaking a mitochondrial danger-STING feed-forward amplifier preserves alveolar-capillary architecture and dampens interferon-chemokine signaling in acute lung injury. (from pulmonology/critical care)
Elmorsy Elsayed A; Amer Maha M; Hamad Rabab S; Abdel-Hamed Mohamed R; Farrag Als — Tissue & cell 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target, mito-ROS-NF-kB, NF-kB-IKK

Demonstrates a mitochondrial danger signal-cGAS/STING-IFN feed-forward loop driving tissue injury and its pharmacological interruption, directly paralleling the BLUE/RED loop mechanism and STING-targeted therapeutics relevant to the SAMHD1 interferonopathy model, though in an acute lung injury rather than SAMHD1 context.
DOI: 10.1016/j.tice.2026.103514

CMPK2 promotes M1 macrophage polarization in sepsis-induced acute lung injury via NLRP3/NF-κB signalling. (from Critical care/pulmonology (sepsis-induced acute lung injury))
Li Cheng; Ding Peng; Zheng Zenglu; Wei Huawei; Yang Yutong — International immunopharmacology 2026
Score: 7/10 | Pathways: NLRP3, NF-kB-IKK, mito-dNTP-transport, nucleotide-rewiring

CMPK2, a key player in the CMPK2-vs-PNC1/2 mitochondrial dNTP supply axis directly implicated in the SAMHD1 mechanism, is shown here to drive NLRP3/NF-κB-mediated macrophage inflammation and mitochondrial ultrastructural damage in sepsis, providing mechanistic support for the CMPK2-mitochondrial-inflammasome link even though SAMHD1 itself is not studied.
DOI: 10.1016/j.intimp.2026.116906

Endosymbiotic theory of aging revisited: Age-related leakage of mitochondrial dsDNA/RNA stimulates cytosolic nucleic acid sensors which remodel the immune network and promote the aging process. (from Evolutionary biology / gerontology)
Salminen Antero; Kaarniranta Kai; Kauppinen Anu — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, AGS-spectrum, other

This review directly supports the BLUE loop mechanism (mtDNA/dsRNA leakage activating cGAS-STING and related sensors driving IFN-I and inflammaging) central to the SAMHD1 A565T pathophysiology, though it addresses general aging rather than SAMHD1 specifically.
DOI: 10.1007/s10522-026-10470-9

Specific bile acids can elicit the type-I interferon response through the cGAS-STING pathway. (from Hepatology/bile acid metabolism)
He Jianan; Huang Ziyan; Xiong Caiwan; Huang Zhicheng; Yan Hao — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target

Demonstrates bile acid-induced mtDNA release via Bax/Bak pores activating cGAS-STING/IFN-I, directly paralleling the BLUE pathway mechanism (VDAC1/mtDNA-cGAS-STING) and connecting to the family's hepatology phenotypes (cholecystectomy clustering, bile acid-innate immunity axis).
DOI: 10.1186/s12964-026-03036-2

Senataxin loss induces cGAS–STING-mediated mitochondrial dysfunction (from Neurology/neurodegeneration (ataxia-AOA2))
Fishburn Judith L.A.; Zhao Hongchang; Fosselman Will; Flores Julian; Wong Megan — preprint (preprint) 2026
Score: 7/10 | Pathways: cGAS-STING, AGS-spectrum, POLG-mtDNA, clinical-phenotype

Demonstrates cGAS-STING-driven mitochondrial dysfunction (ROS, hyperfusion, reduced function) from a distinct genomic instability trigger, directly paralleling the BLUE loop mechanism proposed for SAMHD1 haploinsufficiency and reinforcing the interferon-mitochondrial convergence model.
DOI: 10.64898/2026.06.26.734838

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Targeting IMPDH to inhibit SAMHD1 in KMT2A-rearranged leukaemia. (from Oncology/hematology)
Klootsema Yolande; Tsesmetzis Nikolaos; Sharma Sushma; Hofmann Sophia; Thier Jon — Cell cycle (Georgetown, Tex.) 2026
Score: 6/10 | Pathways: dNTPase, treatment-target

This paper directly studies SAMHD1's dNTPase activity and GTP/dGTP allosteric regulation in the context of leukemia chemotherapy resistance, providing mechanistic insight into SAMHD1 dNTP pool control relevant to the core disease mechanism, though not directly tied to A565T or the interferon-mitochondrial syndrome.
DOI: 10.1080/15384101.2025.2601796

Inhibition of toll-like receptor 4 by allicin suppresses mitochondrial DNA-mediated inflammation and pyroptosis to alleviate myocardial ischemia-reperfusion injury. (from Cardiology)
Liang Shichao; Wu Song; Yin Jiajie; Gao Tong; Liu Mengru — Phytomedicine : international journal of phytotherapy and phytopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

Demonstrates mtDNA leakage driving cGAS-STING and NLRP3-pyroptosis via TLR4 in cardiac ischemia-reperfusion, mechanistically parallel to the BLUE/PURPLE loops and NF-kB priming axis though in a cardiology context rather than SAMHD1-driven interferonopathy.
DOI: 10.1016/j.phymed.2026.158513

Asiatic acid mitigates PM2.5-elicited cardiomyocyte pyroptosis via suppression of mtDNA-driven cGAS-STING-NLRP3 signalling. (from Cardiology/environmental toxicology)
Chen Zefeng; Yu Xianguan; Tang Leile; Zhao Yunyue; Yang Xubin — Journal of cardiovascular pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Demonstrates mtDNA-driven cGAS-STING-NLRP3-pyroptosis cascade in cardiomyocytes and a natural compound that blocks it, directly mirroring the Loop A/B mechanism (VDAC1-independent mtDNA release, TFAM loss, cGAS-STING-NLRP3 axis) relevant to the family's cardiac and interferonopathy phenotype though not SAMHD1-specific.
DOI: 10.1097/FJC.0000000000001858

Dendrobine alleviates lung injury in septic mice by inhibiting mitochondrial-endoplasmic reticulum crosstalk-mediated NLRP3 inflammasome activation. (from critical care/sepsis pharmacology)
Zhang Shichao; Luo Kaihang; Wei Xinyue; Qing Cheng; Zhang Jianguo — Journal of pharmacological sciences 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, treatment-target

Demonstrates VDAC1-centered mitochondrial-ROS/mtDNA release driving NLRP3 activation in macrophages, mechanistically parallel to the BLUE/GOLD loops though via IP3R-GRP75-VDAC1-HK2 glycolytic axis rather than SAMHD1/dGTP.
DOI: 10.1016/j.jphs.2026.05.007

A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment. (from Orthopedics/spine surgery (intervertebral disc degeneration))
Wang Wenchao; Huo Wenxiang; Qian Dingfei; Hou Peihong; Su Cheng — Bioactive materials 2026
Score: 6/10 | Pathways: NLRP3, treatment-target, mito-ROS-NF-kB

Describes a mtDNA leakage-cfDNA-NLRP3 inflammasome axis with MCC950 (a named NLRP3 inhibitor in the syndrome's mechanism) as therapeutic, offering a mechanistic and pharmacologic parallel to Loop B/NLRP3 activation despite different disease context.
DOI: 10.1016/j.bioactmat.2026.05.027

Silibinin restricts mitochondria-associated inflammatory pathways in LPS-stimulated murine microglia BV2 through TREM2. (from Neuroinflammation/pharmacology)
Chen Wenhui; Wang Xiaoling; Liu Panwen; Kang Yu; Hayashi Toshihiko — Cellular immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

This paper demonstrates a natural compound restoring mitochondrial quality control to suppress STING and NLRP3 inflammasome activation in microglia, directly relevant to the core mitochondrial-inflammatory pathways implicated in the syndrome, though not SAMHD1-specific.
DOI: 10.1016/j.cellimm.2026.105102

Cellular copper overload mediates senescence-associated secretory phenotype induction in BV2 microglia following lead and copper exposure. (from Toxicology/Neurodegeneration)
Wang Tao; Chen Chao; Li Ran; Su Li-Hong; Tian Hao-Jie — Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB

Demonstrates mtDNA release triggering cGAS-STING-NLRP3 axis via ROS in microglia, mechanistically paralleling the VDAC1/cGAS-STING-NLRP3 (Loop A/B) pathways central to this disease model, though driven by heavy metal toxicity rather than SAMHD1 dysfunction.
DOI: 10.1016/j.fct.2026.116068

cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis. (from Neurology)
Zhang Jiajie; Li Jiarui; Li Yanan; Liu Chunxiao; Shi Lei — Neural regeneration research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, AGS-spectrum

Reviews cGAS-STING/IFN-I-driven neuroinflammation and its therapeutic targeting (including ataxia-telangiectasia, an interferonopathy-adjacent condition), directly relevant to Loop A and the AuDHD/neuro-immune features of the family but not SAMHD1-specific.
DOI: 10.4103/NRR.NRR-D-25-00367

Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis. (from Rheumatology (gout/crystal arthropathy))
Geng Zhijun; Wu Di; Hou Yajing; Kang Lulu; Zhang Xiaofeng — Clinical rheumatology 2026
Score: 6/10 | Pathways: urate-NLRP3, NLRP3

This paper details MSU crystal-induced macrophage lytic death and inflammasome dynamics, directly relevant to the GOLD stream's urate-NLRP3 axis and gout pathogenesis in the mechanism model, though it does not address SAMHD1 or dNTP metabolism.
DOI: 10.1007/s10067-026-08262-0

Nrf2 promotes NLRP3 inflammasome assembly and activation by Klf9-TXNIP axis. (from Rheumatology/immunometabolism)
Zhou You; You Hui; Xia Xin-Yu; Zhang Ke; Jiang Hui — Cell death discovery 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, NF-kB-NLRP3-priming, treatment-target

Describes a novel Nrf2-Klf9-TXNIP mechanism for NLRP3 inflammasome assembly and validates relevance in MSU-crystal gouty arthritis, directly relevant to the GOLD stream and urate-NLRP3 axis in the mechanism map, though not SAMHD1-specific.
DOI: 10.1038/s41420-026-03219-3

SIRT5 desuccinylates PRDX3 to promote its chaperone-mediated autophagy and mitigate mitochondrial dysfunction in MSU crystal-induced inflammation. (from Rheumatology/gout biochemistry)
Deng Yaxin; Yu Kailin; Ou Lijun; Wang Ling; Cai Yuanze — International immunopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, mito-ROS-NF-kB, treatment-target

This paper details MSU crystal-induced mitochondrial dysfunction driving NLRP3 activation via PRDX3 accumulation, directly relevant to the GOLD stream (dGTP-purine catabolism-uric acid-MSU-NLRP3) in the disease model, though it does not involve SAMHD1 or interferon signaling.
DOI: 10.1016/j.intimp.2026.117064

SLC16A9-mediated uric acid uptake promotes myocardial hypertrophy in dilated cardiomyopathy via NLRP3 inflammasome activation. (from Cardiology)
Hu Zhi; Ding Yiming; Wang Tingzhong; Hou Xiaolin; Song Qiang — Experimental cell research 2026
Score: 6/10 | Pathways: urate-NLRP3, NLRP3, treatment-target

Demonstrates a urate-transporter-driven NLRP3 activation axis (GOLD stream analog) in cardiomyopathy, mechanistically relevant to the uric acid/MSU-NLRP3 route implicated in the SAMHD1 syndrome and to potential cardiac phenotype in carriers.
DOI: 10.1016/j.yexcr.2026.115085

Design, semi-synthesis and biological evaluation of grandiflorenic acid derivatives as potent covalent NLRP3 inhibitors. (from medicinal chemistry/pharmacology)
Pérez-Rodríguez Daniel; Amesty Ángel; Oramas-Royo Sandra; Fernández-Vega Eva; Cu — European journal of medicinal chemistry 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Describes novel covalent small-molecule NLRP3 inhibitors effective across multiple activation stimuli (including MSU crystals), representing a potential therapeutic strategy directly relevant to the NLRP3 hyperactivation central to the SAMHD1 A565T interferon-mitochondrial syndrome.
DOI: 10.1016/j.ejmech.2026.118935

Baricitinib in Two Pediatric Patients with COPA syndrome: A Case Series and Literature Review. (from Pediatric rheumatology/pulmonology)
Villarreal Enrique G; Dissanayake Dilan; Laxer Ronald M; Yip Kenneth W; Kritzing — Modern rheumatology case reports 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, AGS-spectrum, clinical-phenotype

COPA syndrome is a type I interferonopathy treated with baricitinib (JAK inhibitor), directly paralleling the IFN-I/JAK-STAT treatment strategy relevant to SAMHD1-driven interferonopathy in this family.
DOI: 10.1093/mrcr/rxag052

Loss of the kinases TBK1 and IKKε sensitizes target cancer cells to T cell killing through an IFN-γ-mediated inflammatory death program. (from cancer immunology/immuno-oncology)
Sun Nicholas D; Carr Allison R; Krogman Erica N; Chawla Yogesh; Zhong Jun — Science signaling 2026
Score: 6/10 | Pathways: NF-kB-IKK, JAK-STAT, treatment-target, other

Demonstrates TBK1/IKKε (non-canonical NF-kB/IFN kinases central to the disease's NF-κB-IKK crosstalk axis) as inhibitors of RIPK1-dependent inflammatory death and NF-κB activation, revealing a mechanistic link between IFN signaling, NF-κB, and cell death that is adjacent to the interferon-mitochondrial-NF-κB circuitry implicated in the SAMHD1 syndrome, though not SAMHD1-specific.
DOI: 10.1126/scisignal.adz7366

Targeting the cGAS-STING pathway alleviates neuroinflammation and cognitive impairment induced by chronic infection of Toxoplasma gondii. (from Neurology/Infectious Disease (parasitology-neuroinflammation))
Xing Yihui; Lv Huiling; He Peixuan; Xu Yongyao; Shen Weifan — Journal of neuroinflammation 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

Demonstrates cGAS-STING pathway activation driving neuroinflammation, senescence/SASP, and cognitive impairment in a chronic infectious trigger model, mechanistically relevant to the IFN-I/BLUE loop and neurologic/AuDHD phenotype axis though not SAMHD1-specific.
DOI: 10.1186/s12974-026-03937-6

Tegument protein UL16 of herpes simplex virus 1 suppresses the innate immune response by downregulating MAVS abundance via mitophagy. (from virology/microbiology (HSV-1 immune evasion))
Wang Jingwen; Zhu Rongli; Yi Ping; Gan Mengyao; Long Feng — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, other

This paper shows a viral tegument protein degrading MAVS via FUNDC1-mediated mitophagy to suppress RLR/IFN-I signaling, providing mechanistic insight into virus-induced mitophagy-immune crosstalk that parallels the mitophagy-block/interferon axis relevant to SAMHD1-driven interferonopathy and post-viral ME/CFS triggers.
DOI: 10.1080/15548627.2026.2698747

GAMG alleviates silicosis inflammation and fibrosis by targeting STING. (from Pulmonology/occupational medicine (silicosis))
Zhang Jing; Xang Miaoqing; Yao Zongze; Shao Wei; Liu Zhiyu — Ecotoxicology and environmental safety 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This paper demonstrates STING/TBK1/NF-κB pathway activation via cytosolic dsDNA driving inflammation and fibrosis, directly relevant to the BLUE loop (cGAS-STING-IRF3-IFN-I) and NF-κB crosstalk mechanisms central to the SAMHD1 syndrome, and identifies a small-molecule STING inhibitor (GAMG) with therapeutic implications.
DOI: 10.1016/j.ecoenv.2026.120405

Dexamethasone activates anti-tumor immunity in multiple myeloma by dismantling the GR-PPP1CB complex to restore STING/IRF3 signaling. (from Oncology (multiple myeloma immunotherapy))
Wang Chen; Liu Lingling; Zhang Jiale; Sun Shanliang; Lv Xinyu — Journal for immunotherapy of cancer 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

This paper details TBK1-IRF3/STING pathway modulation via GR-PPP1CB in multiple myeloma, directly intersecting with the core interferon-STING axis (Loop A) relevant to SAMHD1 mechanism and the family's multiple myeloma phenotype, though not SAMHD1-specific.
DOI: 10.1136/jitc-2026-015256

BRCA1 deficiency induces NFκB-dependent type-I interferon signaling in fallopian tube epithelial cells. (from Gynecologic oncology (BRCA1/fallopian tube epithelium))
Madaan Vidushi; Kollara Alexandra; Spaner David; Brown Theodore J — Neoplasia (New York, N.Y.) 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, JAK-STAT, treatment-target

Demonstrates cGAS-STING-TBK1-IRF3 driven type-I interferon signaling (ISG15/USP18) with NF-kB permissive crosstalk in a DNA-damage/genome-instability context, mechanistically analogous to the SAMHD1-driven IFN-I/NF-kB axis and relevant to oncology surveillance in carrier families.
DOI: 10.1016/j.neo.2026.101320

ANXA2 suppresses antiviral immunity by impeding STING Golgi translocation and disrupting the TBK1/IKKε-IRF3 axis. (from Virology/molecular microbiology)
Liu Hongyang; Xue Mengdi; Feng Chunying; Yu Jimin; Ye Guangqiang — Journal of virology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK

Details a novel negative regulator (ANXA2) of the cGAS-STING-TBK1/IKKε-IRF3 axis central to the BLUE loop IFN-I pathway implicated in SAMHD1 haploinsufficiency pathophysiology, though not disease-specific.
DOI: 10.1128/jvi.02081-25

Loss of cGAS facilitates angiogenesis in diabetic foot ulcer healing by suppressing the STING/ferroptosis pathway. (from Endocrinology/Wound Healing (Diabetic Foot Ulcer))
Li Wei; Kang Mengyang; Zhang Guofeng; Hu Huishe; Qin Hao — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates cGAS-STING-TBK1-IRF3-NFkB axis driving pathology (ferroptosis, angiogenesis suppression) in a metabolic/vascular disease context, offering mechanistic and therapeutic parallels relevant to the interferon-mitochondrial syndrome's core signaling loop though not SAMHD1-specific.
DOI: 10.1016/j.intimp.2026.116684

EXOC5/SEC10 attenuates antiviral IFN-I signaling by targeting STING1 for autophagic degradation. (from Virology/molecular cell biology (autophagy trafficking))
Ma Wenqing; Xu Yanan; Yu Jie; Sun Fachao; Yu Xiao — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Describes a novel negative-feedback regulator (EXOC5-TRIM56-STING1-SQSTM1 autophagic degradation axis) of the cGAS-STING/IFN-I pathway central to the BLUE loop, offering mechanistic and therapeutic insight relevant to interferon dysregulation but not SAMHD1-specific.
DOI: 10.1080/15548627.2026.2659292

Emodin alleviates radiation-induced pulmonary fibrosis by targeting cellular senescence via the mtDNA-cGAS-STING axis. (from Pulmonology/radiation oncology)
Duan Wei; Sha Yanling; Tang Xi; Liu Riu; Su Bin — 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

Demonstrates mtDNA leakage-driven cGAS-STING-NF-κB activation and mitochondrial ROS as drivers of senescence/fibrosis, directly paralleling the BLUE/RED loop mechanisms in the SAMHD1 syndrome and offering a pharmacologic (emodin) precedent for pathway-targeted intervention.
DOI: 10.1007/s10522-026-10472-7

The novel PARP-1 inhibitor BMMP-TSC bridges mitochondrial dysfunction and innate immunity via mtDNA leakage and cGAS-STING to suppress breast cancer. (from Oncology/pharmacology (PARP-inhibitor drug development))
Wang Nan; Huang Jianting; Fei Fengshu; Ma Shiyu; Fu Qianlong — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mtDNA leakage-driven cGAS-STING activation from mitochondrial damage in a cancer context, mechanistically parallel to the BLUE loop but in an oncology/PARP-inhibitor setting rather than SAMHD1-driven interferonopathy.
DOI: 10.1016/j.cbi.2026.112247

Neutrophil extracellular traps in gout, rheumatoid arthritis, and systemic lupus erythematosus: Mechanistic heterogeneity and therapeutic implications. (from Rheumatology)
Chen Haixu; Liu Xia; Guo Changying; Song Chao; Zeng Lianlin — Tissue & cell 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, cGAS-STING, clinical-phenotype

Discusses ox-mtDNA-driven cGAS/STING/IFN-I and NLRP3 activation in gout/RA/SLE, mechanistically parallel to the GOLD/BLUE loops and relevant to the family's rheumatoid arthritis and gout-adjacent phenotypes, though NETosis is not directly implicated in the SAMHD1 mechanism.
DOI: 10.1016/j.tice.2026.103735

Selective induction of mitochondrial fragmentation for cancer immunotherapy via mtDNA-Targeting AIE photosensitizer. (from Oncology/photodynamic nanomedicine)
Wang Wen-Jin; Hao Ying-Xin; Wang Yu-Meng; Xin Zhuo-Yang; Zhang Man — Biomaterials 2026
Score: 5/10 | Pathways: NLRP3, VDAC1, treatment-target

Demonstrates mtDNA release via mitochondrial permeability transition triggering NLRP3-GSDMD pyroptosis, mechanistically overlapping with the disease's Loop A/B mitochondrial-inflammasome axis, but in a cancer photodynamic therapy context rather than SAMHD1 biology.
DOI: 10.1016/j.biomaterials.2026.124211

Targeting Cathepsin B with p-coumaric acid rescues WWP1-dependent proteasomal degradation of NLRP3 in hyperuricemic nephropathy. (from Nephrology/pharmacology)
Li Fengqin; Wang Yanzhe; Liu Xia; Wu Yue; Miao Naijun — Molecular medicine (Cambridge, Mass.) 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

This paper details a urate/NLRP3-driven nephropathy mechanism (GOLD stream analog) and a novel NLRP3 proteasomal degradation pathway, offering an adjacent but non-interferon mechanistic link and a potential therapeutic angle relevant to the gout/uric acid axis in the disease profile.
DOI: 10.1186/s10020-026-01544-y

Exploration of the Potential Mechanism of Clematichinenoside AR in Alleviating Hyperuricemia Based on Untargeted Metabolomics and Nrf2 Signaling Pathway. (from Pharmacology/Nephrology (traditional Chinese medicine metabolomics))
Liang Qi; Lu Heng; Dong Hongjing; Yu Jinqian; Li Tao — Rapid communications in mass spectrometry : RCM 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

This paper demonstrates the GOLD pathway (purine catabolism → uric acid → NLRP3) mechanistically via a natural compound reducing xanthine oxidase, uric acid, and NLRP3/Caspase-1 activation, relevant to the SAMHD1 syndrome's independent gout/urate-NLRP3 axis but not SAMHD1-specific.
DOI: 10.1002/rcm.70109

Lorlatinib protects dopaminergic neurons by inhibiting ALK-mediated neuroinflammation in a mouse model of Parkinson's disease. (from Neurology/Parkinson's disease pharmacology)
Kim Do-Yeon; Kim Seong-Eun; Park Jung-Eun; Leem Yea-Hyun; Park Jin-Sun — Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 5/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates STING-TBK1-IRF3/NF-κB neuroinflammatory axis and microglial activation in a neurodegeneration model, mechanistically overlapping with the interferon-NF-κB crosstalk relevant to the SAMHD1 syndrome's neurological/AuDHD phenotypes, though not SAMHD1-specific.
DOI: 10.1016/j.biopha.2026.119596

Pharmacological inhibition of STING-TBK1 signaling is associated with reduced PANoptosis-like features and fibrotic remodeling in keloids. (from Dermatology/plastic surgery (fibroproliferative skin disorders))
Wang Xinyue; Tian Yuan; Luo Sai; Zhu Wenwen; Zhu Yangdong — International immunopharmacology 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates STING-TBK1-IRF3 signaling driving inflammatory programmed cell death and fibrosis in keloids, offering a tangential mechanistic parallel (STING/TBK1 activation and pharmacological inhibition) but no direct link to SAMHD1, mitochondrial dNTP dysregulation, or the family phenotype spectrum.
DOI: 10.1016/j.intimp.2026.116869

Saturated mutagenesis screen of M-MLV reverse transcriptase identifies variants enhancing prime editing efficiency (from Molecular biology/genome engineering)
Li Hui; Wang Yifan; Zhang Chenxin; Tun Thi Thi; Yu Shi — preprint (preprint) 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper improves prime editing efficiency via M-MLV RT engineering, a generic gene-correction technology platform relevant to future correction of the SAMHD1 A565T missense variant but with no immune/myeloid cell-type specificity or disease-specific demonstration.
DOI: 10.64898/2026.07.06.736660

Systematic profiling of PE6 variants establishes generalizable principles for efficient and specific prime editing (from genome engineering/molecular biology)
Shin Kyuwon; Shin Ju-Young; Woo Aram; Han Dabin; Lee Beomjun — preprint (preprint) 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper advances prime editing efficiency/specificity (PE6 variants, DeepPrime6), a generalizable gene-correction technology platform potentially applicable to correcting the SAMHD1 A565T missense variant but not disease-specific or immune-cell targeted.
DOI: 10.21203/rs.3.rs-10000319/v1

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Targeted Treatment for Hyperuricemia: The Drug Pipeline. (from Rheumatology/geriatrics (gout pharmacotherapy))
Barry Austin; Helget Lindsay N; Mikuls Ted R — Drugs & aging 2026
Score: 4/10 | Pathways: urate-NLRP3, treatment-target

This is a clinical gout pharmacology review touching the GOLD pathway (uric acid/NLRP3) and NLRP3-targeted therapy but does not address SAMHD1, dGTP-driven purine catabolism, or interferon-mitochondrial mechanisms specifically.
DOI: 10.1007/s40266-026-01313-w

The Dual Role of Exosomes in Gout: From Inflammatory Amplifiers to Therapeutic Regulators. (from Rheumatology)
Gao Xuege; Zhang Jiawei; Kong Xiaojuan; Xue Yanli; Fan Weimin — Inflammation 2026
Score: 4/10 | Pathways: urate-NLRP3, NLRP3

Discusses MSU crystal-driven NLRP3 inflammation and exosome biomarkers in gout, touching the GOLD stream endpoint but without SAMHD1, IFN, or mitochondrial mechanistic linkage.
DOI: 10.1007/s10753-026-02551-1

Emapalumab plus conventional therapy with or without ruxolitinib for pediatric hemophagocytic lymphohistiocytosis: a single center retrospective study. (from pediatric hematology-oncology)
Liao Meiling; Xiao Li; Gu Min; Yu Jie — Immunologic research 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Describes ruxolitinib (JAK1/2 inhibitor) use in a hyperinflammatory cytokine syndrome (HLH), tangentially relevant to JAK-STAT/IFN pathway therapeutics but not directly tied to SAMHD1 mechanism or family phenotypes.
DOI: 10.1007/s12026-026-09801-2

Two novel kindreds with autosomal recessive STAT2 deficiency. (from Pediatric immunology/infectious disease (inborn errors of immunity))
Kienapfel Verena; Cresens Lotte; Bizien Lucy; Vasconcelos Julia; Chbihi Marwa — Journal of human immunity 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

STAT2 deficiency is a downstream node of the same type I IFN/JAK-STAT axis relevant to the interferonopathy mechanism and uses ruxolitinib as in the family's proposed treatment context, but is a distinct autosomal recessive disease unrelated to SAMHD1 haploinsufficiency.
DOI: 10.70962/jhi.20260037

The role of NLRP3 inflammasome in opioid-induced neurochemical markers, therapeutic effects, and adverse effects in male mice. (from Neuropharmacology/addiction medicine)
Rodriguez Myosotys; Veeragoni Dileepkumar; Carbajal Candy; Owens Florida; Eans S — Brain, behavior, and immunity 2026
Score: 4/10 | Pathways: NLRP3, NF-kB-NLRP3-priming, treatment-target

This paper demonstrates NLRP3/NF-kB/MAPK-driven neuroinflammation and MCC950 efficacy in an opioid model, offering mechanistic and pharmacological parallels (MCC950 as NLRP3 inhibitor) but no direct SAMHD1, interferon, or mitochondrial dNTP connection.
DOI: 10.1016/j.bbi.2026.106528

Persistence of large mtDNA rearrangements linked to premature aging in Pol γ exonuclease-deficient mice. (from Mitochondrial genetics/aging biology)
Wu Shilan; Lujan Scott A; Burkholder Adam B; Nissanka Nadee; Longley Matthew J — Nucleic acids research 2026
Score: 4/10 | Pathways: POLG-mtDNA, other

Demonstrates POLG exonuclease-deficiency driving large mtDNA deletions/rearrangements and premature aging, mechanistically adjacent to the PURPLE pathway's POLG-stalling/ox-mtDNA node but without any SAMHD1, dNTP pool, or immune signaling connection.
DOI: 10.1093/nar/gkag648

Precision gene editing: From proof-of-concept to curative therapies. (from Gene therapy/genetic medicine)
Cui Tongtong; Li Bojin; Cai Bingyu; Wang Hui; Li Wei — Trends in molecular medicine 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General review of precision gene editing technologies and clinical translation with no specific mention of SAMHD1 or immune/myeloid cell targeting relevant to correcting a het missense variant like A565T.
DOI: 10.1016/j.molmed.2026.06.004

Prime editing-mediated microhomology enables efficient replacement of large DNA. (from Genome engineering / synthetic biology)
Xie Yuyang; Li Pan; He Zhiyong; Huang Honglin; Wu Dingzhou — Nucleic acids research 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This describes a general-purpose prime editing method for large DNA replacement without disease-specific or immune/myeloid cell application, offering only generic future relevance to correcting the SAMHD1 A565T variant.
DOI: 10.1093/nar/gkag626

Emerging frontiers in genome editing: From CRISPR to next-generation technologies. (from Molecular biology/biotechnology (genome engineering))
Mishra Saurabh; Rehan Samrah; Barekzai Ahmad Mujtaba; Sharma Ambika; Raghav Alok — Methods (San Diego, Calif.) 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

A general review of genome editing technologies (CRISPR, base/prime editing, delivery systems) with only broad, non-specific relevance to future SAMHD1 A565T correction strategies rather than direct mechanistic or clinical data.
DOI: 10.1016/j.ymeth.2026.05.011

Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in the HBG1/2 promoters. (from Hematology/gene therapy)
Chalumeau Anne; Antoniou Panagiotis; Bou Dames Maria; Martinucci Pierre; Retana * — Molecular therapy. Nucleic acids 2026
Score: 4/10* | Pathways: gene-therapy-delivery, prime-editing

Demonstrates prime-editing and CRISPR-HDR correction in HSPCs for sickle cell disease, offering methodological relevance to future SAMHD1 missense correction strategies but no direct SAMHD1/interferon-mitochondrial pathway connection.
DOI: 10.1016/j.omtn.2026.102974

Enhancing prime editing by fusing polymerase substrate-binding proteins to reverse transcriptase. (from molecular genome engineering / biochemistry)
Zhao Dongdong; Wang Ting; Zhang Lu; Sha Taixin; Zhao Xiumei — Nucleic acids research 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a general prime editing efficiency improvement (PSBP fusion to RT) without any immune/myeloid cell targeting or SAMHD1-relevant application, making it only tangentially relevant as a generic gene-correction technology platform.
DOI: 10.1093/nar/gkag657

Naja atra SVPLA2 upregulates hexokinase 2-driven macrophage M1 polarization via the cGAS-STING signaling activation. (from Toxicology/venom pharmacology)
Liu Jiahao; Wen Zejing; Tang Sunkun; Wu Jiajia; Han Xinyi — 2026
Score: 4/10 | Pathways: cGAS-STING, other

Demonstrates mtDNA release triggering cGAS-STING pathway activation in macrophages, mechanistically parallel to the BLUE loop but in an unrelated snake venom toxicology context with no SAMHD1 or NLRP3/interferonopathy linkage.
DOI: 10.1016/j.toxicon.2026.109208

The NF-κB-driven inflammatory cascade in ischemic stroke: Linking DAMPs, inflammasomes, and neurovascular dysfunction. (from Neurology/stroke)
Liu Yuan; Zhang Yun — Gene 2026
Score: 3/10 | Pathways: NLRP3, NF-kB-IKK, cGAS-STING

This is a general ischemic stroke NF-κB/inflammasome review with overlapping pathway components (STING, NLRP3, mtDNA DAMPs) but no connection to SAMHD1, dNTP metabolism, or the family phenotype spectrum.
DOI: 10.1016/j.gene.2026.150163

CGRP-uric acid axis in migraine: A redox-inflammatory framework linking neurovascular signaling and metabolic regulation. (from Neurology (headache/migraine medicine))
Lu Chien-Lin; Cheng Yu-Chen; Lu Kuo-Cheng — Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 3/10 | Pathways: urate-NLRP3, other

This migraine-focused review discusses uric acid/NLRP3/ROS/NF-kB convergence in a neurovascular context, touching the GOLD pathway (urate-NLRP3) but with no SAMHD1, interferon, or mitochondrial dNTP relevance and no clear link to the family phenotype spectrum.
DOI: 10.1016/j.biopha.2026.119709

Exploring the anti-gout mechanism of Erding granules based on network pharmacology and experimental verification. (from traditional Chinese medicine/pharmacology)
Wang Guanglei; He Liang; Zhang Yihua; Tao Xikai — Pakistan journal of pharmaceutical sciences 2026
Score: 3/10 | Pathways: urate-NLRP3

Paper links MSU-induced NLRP3/IL-1β/IL-18 release to a herbal formula via INSR/PRKCA/IGF1R signaling, touching the GOLD pathway (uric acid-NLRP3) but with no SAMHD1, interferon, or mitochondrial dNTP connection.
DOI: 10.36721/PJPS.2026.39.8.232.1

Interpretable machine learning model using peripheral blood for non-invasive detection of moderate-to-severe myelofibrosis in JAK2 V617F-positive MPNs: A multicentre pilot proof-of-concept study. (from Hematology/Oncology (myeloproliferative neoplasms))
Hao Zhuanghui; Song Miaoke; Wang Huichao; Yan Congrui; Cao Shuhua — British journal of haematology 2026
Score: 3/10 | Pathways: NLRP3, treatment-target

IL-1β/NLRP3 involvement in JAK2-mutant myelofibrosis and ruxolitinib response is tangentially related to the interferon-inflammasome axis but concerns a distinct disease (MPN) and gene (JAK2) unrelated to SAMHD1 haploinsufficiency.
DOI: 10.1111/bjh.70552

CD28+ CD8+ Tem cells with a STAT1-dependent glucocorticoid receptor deficit contribute to steroid-refractory acute GVHD. (from Transplant hematology/immunology)
Pan Zengkai; Deng Yujun; Huang Jingtao; Bian Haoxing; Chen Yiyin — Blood 2026
Score: 3/10 | Pathways: JAK-STAT, treatment-target

This paper describes STAT1-GR crosstalk and JAK inhibition in steroid-refractory GVHD, a peripheral JAK-STAT/inflammation mechanism sharing pathway components (STAT1, ruxolitinib) but with no direct link to SAMHD1, cGAS-STING, NLRP3, or mitochondrial dNTP biology.
DOI: 10.1182/blood.2025032587

Metagenomic profiling of gut microbiome in post-cholecystectomy patients with diarrhea: a nested case-control study. (from Gastroenterology/microbiome research)
Ye Jiayi; Mao Peiyu; Li Bo; Hao Ying; Chen Yuwen — BMC microbiology 2026
Score: 3/10 | Pathways: clinical-phenotype

Cholecystectomy clustering is a tracked family phenotype but this paper's gut microbiome/diarrhea findings have no direct mechanistic link to SAMHD1, interferon, or inflammasome pathways.
DOI: 10.1186/s12866-026-05346-4

Maternal gut microbiota mediates prenatal stress-induced fetal blood‒brain barrier dysfunction. (from Obstetrics/neurodevelopmental microbiome research)
Wang Xuanping; Zhou Fang-Yue; Wu Ting; Duan Chenchi; Luo Xukai — Gut microbes 2026
Score: 3/10 | Pathways: pregnancy-fetal, JAK-STAT, other

This paper involves IFN-β signaling and maternal-fetal axis relevant tangentially to interferonopathy biology but lacks any SAMHD1, cGAS-STING, NLRP3, or mitochondrial dNTP mechanism connection.
DOI: 10.1080/19490976.2026.2631242

Targeting the ATX-LPA Axis Overcomes TKI Resistance and Immunosuppression in Renal Cell Carcinoma via Dual Inhibition of AKT/mTOR and TBK1/IRF3 Pathways. (from Oncology (renal cell carcinoma/tumor immunology))
Luo Jinchen; Lin Hansen; Feng Haoqian; Tan Lei; Liu Xi — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 3/10 | Pathways: treatment-target, other

This paper concerns TBK1/IRF3-mediated PD-L1 upregulation in renal cell carcinoma via the ATX-LPA axis, touching the TBK1/IRF3 node shared with the interferonopathy mechanism but in an oncology/immune-evasion context unrelated to SAMHD1 dNTPase biology or mitochondrial dysfunction.
DOI: 10.1002/advs.76352

A novel role of circCPSF6 regulating antiviral innate immunity via miR-665 and PCBP2-IPS-1 axis in IAV infection. (from Virology/RNA biology)
Meher Aparna; Chaudhary Riya; Kumar Himanshu — Molecular therapy. Nucleic acids 2026
Score: 3/10 | Pathways: JAK-STAT, other

This paper describes circRNA-mediated regulation of antiviral IFN signaling (MyD88/STAT2/IKKε/IPS-1) in influenza infection, tangentially touching IFN-I pathway machinery but with no direct SAMHD1, mitochondrial, NLRP3, or inflammasome connection.
DOI: 10.1016/j.omtn.2026.102973

[Effect of electroacupuncture on acute gastric mucosal injury in mice by regulating macrophage polarization mediated by the cGAS-STING signaling pathway]. (from Traditional Chinese medicine / acupuncture research in gastroenterology)
Xu Yuan-Bo; Wang Jing-Ji; Gao Qiu-Jin; Xu Xin-Yue; He Ruo-Nan — Zhen ci yan jiu = Acupuncture research 2026
Score: 3/10 | Pathways: cGAS-STING, other

Uses cGAS-STING signaling terminology but in an unrelated context (electroacupuncture treatment of ethanol-induced gastric mucosal injury and macrophage polarization), with no connection to SAMHD1, mitochondrial dNTP dysregulation, or the interferon-mitochondrial syndrome described.
DOI: 10.13702/j.1000-0607.20251161

Immune cell-intrinsic STING activation drives tumor ferroptosis via AA-mediated suppression of ACSL4 lactylation in colorectal cancer. (from Oncology (colorectal cancer immunometabolism))
Ding Lina; Du Wenqi; Zhu Jing; Zhang Yuxiang; Wang Xingyue — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 3/10 | Pathways: cGAS-STING, other

This paper uses STING signaling in an oncology/ferroptosis context unrelated to SAMHD1, mitochondrial dNTP dysregulation, or interferonopathy syndrome mechanisms, though it touches the STING node relevant to the broader pathway architecture.
DOI: 10.1073/pnas.2524594123

Smart-responsive lentinan-DMXAA conjugate for synergistic STING-mediated pancreatic cancer immunotherapy. (from Oncology/pharmaceutical nanomedicine)
Zhang Zhengxian; Zhu Xin; Cui Jingru; Han Jiale; Wang Jiaxing — International journal of pharmaceutics 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This is a drug-delivery oncology paper exploiting STING agonism (TBK1-IRF3-IFN-beta) for pancreatic cancer immunotherapy, sharing the STING pathway node but with no SAMHD1, mitochondrial, or NLRP3 connection to the syndrome mechanism.
DOI: 10.1016/j.ijpharm.2026.126996

Cellular hnRNP D promotes influenza A virus replication by inhibiting TBK1-IRF3-mediated innate immune response. (from virology/molecular virology)
Xu Chenchen; Peng Yunling; Liu Shuhui; Xie Ran; Feng Duanchenxi — Journal of virology 2026
Score: 3/10 | Pathways: cGAS-STING, other

This paper describes TBK1-IRF3 antagonism by an influenza viral evasion protein, touching the cGAS-STING/IFN-I axis but with no connection to SAMHD1, mitochondrial dNTP pools, or NLRP3 pathways central to this disease.
DOI: 10.1128/jvi.00257-26

Breaking the oncogene-immune suppression cycle through dual HER2 silencing and innate immune activation by biomineralized DNA nanocomplexes. (from Oncology/nanomedicine drug delivery)
Duan Yubei; Huang Jiaxin; Huang Tianping; Yang Kaige; Qi Liwen — Journal of controlled release : official journal of the Controlled Release Society 2026
Score: 3/10 | Pathways: cGAS-STING

Involves cGAS-STING pathway activation but in a cancer nanomedicine context unrelated to SAMHD1 dNTPase biology, mitochondrial dysfunction, or the family phenotype spectrum.
DOI: 10.1016/j.jconrel.2026.115009

The TRIM27/STING Axis Mediates Schisandrin B-Induced Inhibition of Myeloid-Derived Suppressor Cells Accumulation to Potentiate Anti-PD-1 Immunotherapy in Hepatocellular Carcinoma. (from Oncology/immunotherapy)
Huang Lei; Li Siying; Li Ziqing; Qin Zhuo; Sun Yanan — Phytotherapy research : PTR 2026
Score: 3/10 | Pathways: cGAS-STING, other

Involves STING pathway regulation via TRIM27 in cancer immunotherapy context, but focuses on tumor microenvironment/MDSCs in HCC rather than SAMHD1-driven interferonopathy or mitochondrial dysfunction mechanisms.
DOI: 10.1002/ptr.70368

Scoparone inhibits the progression of gastric cancer by regulating the PIN1/STING/TBK1/IRF3 signaling pathway. (from Oncology/pharmacology)
Zhao Na; Wang Ping — Toxicology and applied pharmacology 2026
Score: 3/10 | Pathways: cGAS-STING

Involves STING/TBK1/IRF3 signaling but in the context of gastric cancer drug mechanism unrelated to SAMHD1 or interferonopathy pathophysiology, with STING activation here being tumor-suppressive rather than pathogenic.
DOI: 10.1016/j.taap.2026.117838

Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications. (from biochemistry/enzymology (transglutaminase))
D'Eletto Manuela; Occhigrossi Luca; Colasuonno Fiorella; Bellanca Veronica; Di S — Oncoimmunology 2026
Score: 3/10 | Pathways: cGAS-STING, other

TG2 modulation of TBK1/type I interferon signaling touches tangentially on the IFN-I axis but has no direct connection to SAMHD1, dNTPase, NLRP3, or mitochondrial mechanisms central to this disease profile.
DOI: 10.1080/2162402X.2026.2665505

Viral Infections and Neurodegenerative Diseases: Reinterpreting the Crosstalk Through a Dual-Role Lens. (from neurology/virology gene therapy engineering)
Tahmtan Alireza; Nissapatorn Veeranoot; Saravanabhavan Shanmuga Sundar; Taherkha — Current microbiology 2026
Score: 3/10 | Pathways: gene-therapy-delivery, other

Reviews viral contributions to neurodegeneration and viral vector gene therapy technology broadly, with only tangential overlap to SAMHD1 interferonopathy mechanisms (mitochondrial dysfunction, neuroinflammation) and general gene-editing delivery methods rather than myeloid-targeted correction.
DOI: 10.1007/s00284-026-05018-6

Nanomaterials for subcellular organelle targeting: unlocking new avenues for enhanced therapeutic effectiveness. (from Nanomedicine/drug delivery)
Solouki Kiarash; Sohail Muhammad — Journal of drug targeting 2026
Score: 3/10 | Pathways: gene-therapy-delivery, other

General nanomaterial organelle-targeting review with brief mention of CRISPR/base/prime editing delivery, but no disease-specific mechanistic link to SAMHD1 pathways.
DOI: 10.1080/1061186X.2026.2691784

Re-balancing immunity with CRISPR-Cas9: Novel strategies for cancer and autoimmune disorders. (from genome editing/biotechnology)
Ren Xuanqi; Zhou Ziyang; Kong Lingkai; Guo Yibo; Liu Yan — Biotechnology advances 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery, other

General review of CRISPR-Cas9 strategies (KO/KI/CRISPRa/CRISPRi/base/prime editing) for cancer and autoimmunity is only tangentially relevant as background on gene-editing tools without any SAMHD1, interferon, or mitochondrial pathway content.
DOI: 10.1016/j.biotechadv.2026.108921

Strategies and Advances in Site-Specific Integration of Exogenous Large Genes. (from Genome engineering/gene therapy methodology)
Wu Zhencheng; Chen Jia; Huang Manqi; Hu Wenqi; Liu Yiyu — Human gene therapy 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

This is a general review of large-fragment genomic integration technologies (HDR, prime editing/recombinases, CRISPR transposition) with no specific application to SAMHD1 correction or immune/myeloid cell delivery context relevant to this family's disease.
DOI: 10.1177/10430342261445050

Prime-edited isogenic hiPSC-derived cardiomyocyte model of short QT syndrome type 3 reveals electrophysiological phenotypes and differential drug responses. (from Cardiology/gene-editing methodology)
Kim Min Woo; Park Jeong Hwan; Lee Myeonghee; Lee Seul-Gi; Oh Jeong-Seop — Life sciences 2026
Score: 3/10 | Pathways: prime-editing

This paper demonstrates PE7 prime editing to create an isogenic iPSC-cardiomyocyte channelopathy model, relevant only as a generic gene-editing methodology reference and not to SAMHD1 or immune-mitochondrial pathways.
DOI: 10.1016/j.lfs.2026.124573

Gene Correction Enhances Dopaminergic Cell Therapy in a Nonhuman Primate Model of Parkinson's Disease. (from Neurology/regenerative medicine (gene editing methodology transferable to future SAMHD1 correction strategies))
Yan Qing; Xu Chongchong; Gao Jiangmei; Wang Pu; Wu Qingling — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 3/10 | Pathways: prime-editing

Uses prime editing to correct LRRK2 mutations in iPSC-derived dopaminergic cells for Parkinson's disease, demonstrating gene correction feasibility but unrelated to SAMHD1 mechanism or interferon-mitochondrial pathways.
DOI: 10.1002/advs.76394

Generation and characterization of four iPSC and isogenic gene-corrected lines from Legius syndrome patients. (from stem cell/genetic disease modeling)
der Auweraer Seppe Van; Roth Moritz B; Vlahos Katerina; Howden Sara E; Lockhart * — Stem cell research 2026
Score: 3/10* | Pathways: prime-editing

This paper describes iPSC modeling and CRISPR/prime editing correction of SPRED1 variants in Legius syndrome, unrelated to SAMHD1 or the described interferon-mitochondrial pathways, though it demonstrates prime editing correction methodology potentially analogous to future SAMHD1 variant correction.
DOI: 10.1016/j.scr.2026.104026

Generation of gene-corrected human isogenic iPSC lines from hypertrophic cardiomyopathy patients harboring PRKAG2 mutation (c.2084A>G, p.His530Arg) using prime editing. (from Cardiology / stem cell gene editing)
Lu Zijun; Qiu Zhichao; Zhang Yao; Yang Hao; Yang Yuan — Stem cell research 2026
Score: 3/10 | Pathways: prime-editing

Uses prime editing to correct a heterozygous missense mutation causing a distinct cardiomyopathy (PRKAG2), offering only generic technical analogy to potential SAMHD1 A565T correction strategies rather than direct disease relevance.
DOI: 10.1016/j.scr.2026.104008

New Gene Therapy Strategy for β-Thalassemia. (from Hematology/gene therapy)
Liang Dongguo; Schmidt-Wolf Ingo G H; Pu Jingjing — Stem cell reviews and reports 2026
Score: 3/10 | Pathways: gene-therapy-delivery

Reviews base/prime editing for β-thalassemia gene correction, which is a technology platform of theoretical relevance to future SAMHD1 correction strategies but has no direct mechanistic or clinical overlap with the SAMHD1 interferon-mitochondrial syndrome.
DOI: 10.1007/s12015-026-11132-6

A versatile VLP-mediated CRISPR-RNP platform for precise genome editing and durable epigenome silencing in cancer. (from Oncology/gene therapy delivery engineering)
Ju Sungjin; Lee Jang Hyeon; Yang Jiyun; Jeong Tae Yeong; Choi Chang Geun — Molecular therapy. Nucleic acids 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes a VLP-CRISPR-RNP delivery platform for cancer genome/epigenome editing, relevant only tangentially as a generic delivery technology rather than targeting SAMHD1 correction or immune/myeloid cells specifically.
DOI: 10.1016/j.omtn.2026.102978

Protein Nanocages as Versatile Vectors for Nucleic Acid Delivery: Main Systems and Their Loading Mechanisms. (from nanobiotechnology/bioengineering)
Coffeen Carlos Francisco; Hernández-Gutiérrez Aquetzali Estefanía; Bustos-Jaimes — Molecular biotechnology 2026
Score: 3/10 | Pathways: gene-therapy-delivery

General review of protein nanocage delivery platforms for nucleic acids without specific application to myeloid/immune cells or SAMHD1 correction, only tangentially relevant to future gene therapy translation.
DOI: 10.1007/s12033-026-01564-3

In Utero Gene Therapy for Sickle Cell Disease: Current Evidence, Ethical Considerations, and Future Directions-A Scoping Review. (from Hematology/gene therapy)
Cudjoe Efe; Thorsen Margaret; Molokwu Nneka; Russo Melissa — Clinical therapeutics 2026
Score: 3/10 | Pathways: gene-therapy-delivery, pregnancy-fetal

Discusses in utero gene editing/LNP delivery technology relevant to future SAMHD1 correction strategies but focuses on an unrelated monogenic disease (SCD) with no interferonopathy or mitochondrial mechanism overlap.
DOI: 10.1016/j.clinthera.2026.04.026

Optimizing twin prime editing components for scalable genome editing and therapy in spinocerebellar ataxia type 3. (from Neurology/genetic engineering (gene therapy technology development))
Gwon Lee Wha; Seong Jung Bae; Yeo Hyeon-Gu; Oh Yeounsun; Park Junghyung — Molecular therapy. Nucleic acids 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes twin prime editing optimization for polyQ deletion in SCA3, a general gene-editing technology advance not targeted to SAMHD1, myeloid cells, or immune correction relevant to the disease profile.
DOI: 10.1016/j.omtn.2026.102988

CRISPR-Cas9 Therapeutics in Diabetes Mellitus: From Molecular Mechanisms and Pharmacology to Clinical Development and Translational Barriers (from Endocrinology/diabetes gene therapy)
Kumar Sachin; Singh Harshit; Sharan Lokesh; Jawa Hemangi; Chaturvedi Saurabh — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This paper discusses CRISPR/base/prime editing therapeutics for diabetes with no direct link to SAMHD1 mechanisms, interferonopathy, or the family's mitochondrial-inflammatory phenotype, though it touches generically on gene editing delivery platforms relevant to future SAMHD1 correction strategies.
DOI: 10.22541/authorea.15004994/v1

Pathway Coverage This Week

treatment-target: 43 papers
cGAS-STING: 36 papers
NLRP3: 24 papers
other: 19 papers
gene-therapy-delivery: 17 papers
prime-editing: 15 papers
NF-kB-IKK: 12 papers
urate-NLRP3: 12 papers
mito-ROS-NF-kB: 9 papers
JAK-STAT: 9 papers
clinical-phenotype: 7 papers
AGS-spectrum: 6 papers
VDAC1: 4 papers
nucleotide-rewiring: 2 papers
POLG-mtDNA: 2 papers
NF-kB-NLRP3-priming: 2 papers
pregnancy-fetal: 2 papers
mito-dNTP-transport: 1 papers
dNTPase: 1 papers
ISG15-mitophagy: 1 papers

July 5, 2026
in Weekly Digest, cGAS-STING, POLG-mtDNA, treatment-target, clinical-phenotype
4 min read

SAMHD1 Research Digest — 2026-07-05

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 8 papers evaluated | 4 high-relevance (≥7) | 3 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Early brain-penetrant immunotherapy reverses interferon signature and improves motor outcome in a case of ADAR1-related Aicardi-Goutières syndrome. (from Pediatric Neurology / Neuroimmunology)
Dale Russell C; Hayes Jessica; Han Velda X; Dissanayake Ruwani; Lau Xianzhong — 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, ISG15-mitophagy, AGS-spectrum, treatment-target, clinical-phenotype

This paper directly demonstrates reversal of the type I interferon signature (including downregulation of CGAS, SAMHD1, ISG15, and JAK1) by ruxolitinib + dexamethasone in an AGS interferonopathy, with single-cell RNA-seq validating the same core molecular players central to the SAMHD1 A565T disease mechanism, and provides a clinically actionable brain-penetrant JAK-inhibitor treatment precedent directly applicable to the interferon-driven neurodevelopmental and ME/CFS phenotypes in this family.
DOI: 10.1002/cti2.70113

JAK Inhibition in PNPT1-Related Mitochondrial Interferonopathy: A Case Report and Review of Mitochondrial-Immune Crosstalk. (from Pediatric neurology / mitochondrial medicine)
Brooks Dan Ross; Koh Hyun Yong; Kerrins Taylor Martin; Lang Steven; Bland Emily — 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, POLG-mtDNA, ISG15-mitophagy, treatment-target, clinical-phenotype

This case report directly demonstrates JAK inhibitor (tofacitinib) efficacy in a mitochondrial interferonopathy caused by mt-dsRNA cytosolic leakage activating IFN-I signaling—mechanistically parallel to the SAMHD1 A565T pathway where VDAC1 macropore releases mtDNA to activate cGAS-STING-IRF3-IFN-I-JAK-STAT, and provides clinical proof-of-concept that JAK inhibition can normalize IFN signature and downstream pathology (dystonia, lactate, transaminases) in mitochondrial-immune crosstalk syndromes including AGS-spectrum disease.
DOI: 10.1002/jmd2.70096

Aicardi-Goutières Syndrome: Insights from a Middle Eastern Case Series. (from Pediatric Neurology / Neuroradiology)
Alwalid Osamah; Al Subhi Marwa; Al Serhan Ala Aldeen; Abdulwahhab Saja B; Samran — 2026
Score: 7/10 | Pathways: AGS-spectrum, dNTPase, cGAS-STING, clinical-phenotype, JAK-STAT

This case series directly characterizes SAMHD1-associated AGS in a clinical cohort, including two siblings with a homozygous SAMHD1 variant presenting with chronic arthritis but no neurological disease—a phenotype highly relevant to understanding the genotype-phenotype spectrum of SAMHD1 variants and validating the arthritis/interferonopathy axis central to the family phenotype described.
DOI: 10.3174/ajnr.a9239

SLC30A9-mediated mitochondrial zinc homeostasis drives osteosarcoma chemoresistance by suppressing the mtDNA-cGAS-STING pathway. (from Oncology (osteosarcoma/cancer biology))
Li Hongyu; Yang Biao; Liu Yinliang; Yang Wen; Yu Haoye — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper mechanistically demonstrates that mitochondrial dysfunction → mtDNA cytosolic release via mPTP opening → cGAS-STING activation, directly paralleling the BLUE stream (VDAC1/mtDNA/cGAS-STING axis) central to SAMHD1 haploinsufficiency pathology, and introduces a novel upstream regulator (mitochondrial zinc homeostasis via SLC30A9) of this pathway with therapeutic implications, though the context is osteosarcoma chemoresistance rather than interferonopathy.
DOI: 10.1016/j.lfs.2026.124555

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Myeloid STING restrains cardiac remodeling by suppressing macrophage amyloid precursor protein (from Cardiology)
Natarajan Niranjana; Johny Ebin; Sriram Varsha; Hara Mika; Antwi Praise Ama — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, other

This paper directly demonstrates mtDNA release activating cGAS-STING in cardiac macrophages and reveals a cardioprotective STING-MZF1-APP axis, which is mechanistically adjacent to the BLUE stream (VDAC1→mtDNA→cGAS→STING→IRF3) and relevant to the cardiology phenotype dimension of the disease profile, though the STING function here is tissue-protective rather than interferonopathic and SAMHD1 is not mentioned.
DOI: 10.64898/2026.07.01.735895

Daphnetin alleviates influenza pneumonia by enhancing chaperone-mediated autophagy of KEAP1 through Heat shock cognate 71 kDa protein. (from Pulmonology / natural product pharmacology)
Wang Jian; Liu Huan; Pan Xuanhao; Liu Tianyu; Li Qianyuan — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, mTOR-lysosomal, treatment-target, ME-CFS, other

This paper directly demonstrates that mtDNA leakage activates cGAS-STING inflammation in macrophages during viral pneumonia, and describes a therapeutic axis (HSC70-CMA-NRF2) that mitigates mitochondrial oxidative stress and mtDNA escape—mechanistically adjacent to the BLUE and RED streams of the SAMHD1 interferonopathy model—with potential relevance to the post-viral (ME/CFS) and cGAS-STING-driven IFN-I amplification loops, though SAMHD1, VDAC1, NLRP3, ISG15, or dNTP biology are not addressed.
DOI: 10.1016/j.phymed.2026.158517

Gut Microbiota-Derived TMAO Drives MC3T3-E1 Senescence and Osteogenic Dysfunction via cGAS-STING-NF-κB Signaling: Implications for Age-Related Bone Loss. (from Bone biology / osteoporosis / geriatrics)
Li Lingling; Li Xinsai; Jin Mingming; Zhang Yangyang; Bai Jia — 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, other

This paper demonstrates that mtDNA cytosolic escape activates cGAS-STING-NF-κB to drive cellular senescence, directly implicating the BLUE-stream mechanism central to SAMHD1 haploinsufficiency pathology, but in an osteoblast/bone-loss context with no connection to SAMHD1, interferonopathy, or the family's specific phenotypes.
DOI: 10.1007/s00223-026-01567-x

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

The mitochondrial protease, LonP1, is a potential cardioprotective target for attenuating doxorubicin-induced cardiomyocyte death. (from Cardiology/Oncology)
O'Dwyer Kienan P; Bauer Perry E; Dziadowicz Sebastian A; Pal Subhankhi; Eminhize — 2026
Score: 4/10 | Pathways: POLG-mtDNA, cGAS-STING, VDAC1, clinical-phenotype, other

This paper addresses mtDNA release from damaged mitochondria activating inflammatory and apoptotic signaling (relevant to the BLUE/PURPLE streams via cytosolic mtDNA → cGAS-STING and VDAC1 macropore concepts), but the context is doxorubicin cardiotoxicity and LonP1 protease biology rather than SAMHD1 haploinsufficiency, interferonopathy, or any core family pathway, making the connection tangential despite mechanistic overlap in mtDNA leakage.
DOI: 10.1186/s12967-026-08537-9

Pathway Coverage This Week

cGAS-STING: 8 papers
POLG-mtDNA: 6 papers
other: 5 papers
treatment-target: 4 papers
clinical-phenotype: 4 papers
VDAC1: 4 papers
JAK-STAT: 3 papers
AGS-spectrum: 3 papers
ISG15-mitophagy: 2 papers
dNTPase: 1 papers
mTOR-lysosomal: 1 papers
ME-CFS: 1 papers

June 28, 2026
in Weekly Digest, cGAS-STING, VDAC1, POLG-mtDNA, treatment-target
6 min read

SAMHD1 Research Digest — 2026-06-28

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 12 papers evaluated | 6 high-relevance (≥7) | 5 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Fibroblast Mitochondrial Ca2+ Overload Drives Skin Fibrosis via mtDNA Leakage and cGAS-STING Activation in Systemic Sclerosis. (from Rheumatology/connective tissue disease (systemic sclerosis))
Zhang Xiaoyun; Wang Yingyu; Huang Hai; Guo Xinyi; Ye Wenjing — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the VDAC1 oligomerization → cytosolic mtDNA leakage → cGAS-STING activation axis in a fibrotic disease context, mechanistically validating the BLUE stream of the SAMHD1 haploinsufficiency model, and identifies VDAC1 inhibition and STING inhibition (H-151) as therapeutic targets with in vivo efficacy—highly actionable for the treatment-target framework.
DOI: 10.1002/art.70261

Delphinidin targets voltage-dependent anion channel 1 to inhibit ferroptosis and protect against retinal photochemical damage. (from Ophthalmology/retinal biology)
Wang Hansheng; Li Keyi; Pu Haomou; Xiong Yaoyao; Luo Dan — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates the VDAC1 oligomerization → cytosolic mtDNA leakage → cGAS-STING activation axis that is central to the BLUE stream of the disease mechanism, and identifies delphinidin as a direct VDAC1-targeting compound that interrupts this cascade, making it highly relevant as both a mechanistic validation and a potential therapeutic lead analogous to VBIT-4.
DOI: 10.1016/j.phymed.2026.158455

Interrupting a mitochondrial DNA-driven innate immune circuit attenuates hepatic tissue remodeling and fibrotic architecture in experimental steatohepatitis. (from Hepatology)
Hamad Rabab S; Mohammed Sura Akram; Hasan Waseem Ali; AbuoHashish Norhan Ahmed; * — 2026
Score: 8/10* | Pathways: cGAS-STING, NLRP3, ISG15-mitophagy, IRF7-metabolic, POLG-mtDNA, treatment-target, clinical-phenotype

This paper directly interrogates the mtDNA-cGAS-STING-IRF3-IFN-β axis combined with NLRP3/IL-1β inflammasome and mitophagy (PINK1/Parkin) blockade in a metabolic liver disease model—mapping precisely onto the BLUE, RED, and PURPLE mechanistic streams of the SAMHD1 A565T interferonopathy, and demonstrating that dual upstream (mitophagy enhancement via urolithin A) plus downstream (STING inhibition via C176) targeting produces synergistic multi-domain control, providing directly translatable therapeutic logic for the hepatic steatosis phenotype documented in the family.
DOI: 10.1016/j.tice.2026.103733

Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation. (from Cell biology / organelle biology)
Zhang Qingqi; Gao Junyan; Yang Yiting; Guo Ping; Gao Huiqin — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, treatment-target

This review directly covers the MAM as a hub integrating cGAS-STING activation, NLRP3 inflammasome, mtDNA release via mitochondrial fission/fusion dynamics, and mitophagy/autophagy flux—all four core pathways (PURPLE, BLUE, RED, GOLD) of the SAMHD1 A565T disease mechanism—and explicitly identifies the self-reinforcing cycle between MAM dysfunction and innate immune overactivation that underlies the proposed interferonopathy, making it highly mechanistically relevant even without direct SAMHD1 mention.
DOI: 10.1186/s12964-026-03013-9

Suppression of STING by Acacetin attenuates renal fibrosis via balancing mitophagy and protective nucleoid-phagy. (from Nephrology/Traditional Chinese Medicine pharmacology)
Gao Yujiu; Mu Linjie; Liu Chen; Zhao Yue; Cai Rui — 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, treatment-target, mTOR-lysosomal

This paper directly investigates STING inhibition restoring mitophagy flux and mitochondrial quality control in a fibrotic context, directly relevant to the BLUE and RED pathway loops where cGAS-STING activation and mitophagy blockade drive the interferonopathy cycle in SAMHD1 haploinsufficiency; Acacetin's direct STING binding (Kd=1.57µM) and restoration of autophagic/mitophagic flux represent a novel small-molecule treatment-target insight.
DOI: 10.1016/j.jep.2026.122094

A negative regulator of mitochondrial complex I assembly adapts respiration to cellular energy demand. (from Mitochondrial cell biology / bioenergetics)
Li Zhirong; Chen Nuo; Zhou Caixia; Xu Lingna; Wang Xiyuan — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, other

TMEM141 regulates Complex I assembly and its deficiency causes oxidative mtDNA damage and mtDNA release activating cGAS-STING, directly engaging the BLUE stream of the disease mechanism where cytosolic mtDNA fragments drive cGAS→STING→IRF3→IFN-I, while the Complex I/OXPHOS connection links to the mitochondrial dysfunction central to the PURPLE and RED streams, offering a novel regulatory node (TMEM141/TIMMDC1/AFG3L2/YME1L1 axis) upstream of mtDNA escape.
DOI: 10.1016/j.molcel.2026.06.018

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Role and mechanism of nitric oxide-regulated cGAS/STING pathway-mediated inflammatory response in hypoglycemia-induced coronary artery endothelial cell injury. (from Cardiology/Endocrinology)
Luo Wenping; Wei Xiao; Xiao Qian — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, clinical-phenotype, treatment-target

This paper demonstrates a mechanistic link between mitochondrial damage, mtDNA release, and cGAS/STING pathway activation in coronary endothelial cells—directly overlapping with the BLUE and PURPLE streams of the SAMHD1 haploinsufficiency model—and validates STING inhibition as a cardioprotective strategy, which is relevant to the cardiology clinical context of the family phenotype.
DOI: 10.1371/journal.pone.0350983

cGAS-STING Pathway Mediates Retinal Pigmental Epithelial Dysfunction in Diabetic Retinopathy. (from Ophthalmology/Retinal medicine)
Zhu Zhaoqi; Qiu Aowang; Wang Ningyu; Zhu Ziyu; Yin Wenjie — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates the mechanistic link between mitochondrial DNA leakage, cGAS-STING pathway activation, and downstream inflammation in a non-immune tissue context, validating the BLUE stream mechanism (mtDNA → cGAS → STING → inflammation) and showing STING inhibition as a pharmacological strategy, which is highly relevant to the core interferonopathy mechanism of SAMHD1 haploinsufficiency, though the disease context (diabetic retinopathy) is not directly related to the family phenotype.
DOI: 10.2337/db25-0128

GPAM mediates mitochondrial dysfunction and the progression of alcoholic liver disease through lipid remodeling. (from Hepatology)
Zhan Zibin; Liu Xuewen; Li Zehua; Qiao Xueyan; Li Shuo — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, NLRP3, clinical-phenotype

This paper directly demonstrates that ceramide accumulation and cardiolipin loss disrupt mitochondrial dynamics and impair mitophagy, releasing mitochondrial DNA that activates cGAS-STING-driven inflammation—mechanistically mirroring the BLUE and RED pathway streams in SAMHD1 haploinsufficiency, and invoking ceramide (a named molecular player) alongside impaired mitophagy, though the context is alcoholic liver disease rather than interferonopathy.
DOI: 10.1126/sciadv.aef1896

Neuronal YTHDF2 suppresses innate immune activation in Aβ pathology by promoting m6A-dependent decay of cytosolic mitochondrial mRNAs. (from Neuroscience/Alzheimer's disease research)
Pan Wenqi; Yang Lin; Zhang Yao; Chen Yan; Xu Yuesi — 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, ME-CFS, AGS-spectrum, other

This paper describes cytosolic mitochondrial RNA fragments activating innate immune signaling (RIG-I-MAVS → IFN-β → JAK-STAT neuroinflammation), a parallel mechanism to the VDAC1/cGAS-STING axis in the disease profile where cytosolic mt-derived nucleic acids drive type I interferon responses, reinforcing the concept that mitochondrial nucleic acid escape is a convergent driver of interferonopathy relevant to the SAMHD1 syndrome's neurological and inflammatory phenotypes.
DOI: 10.1126/sciadv.adz0887

RBM10 Deficiency Promotes Anti-PD-1 Resistance in LUAD via STING Alternative Splicing-Driven CCL7 Signaling and Macrophage Polarization. (from Oncology/thoracic)
Gao Weitong; Wang Ruqiong; An Bo; Qi Lishuang; Jing Zihan — 2026
Score: 5/10 | Pathways: cGAS-STING, other

This paper identifies a STING alternative splicing mechanism (exon 3 exclusion) that modulates cGAS-STING signaling output and feeds into a mtDNA-cGAS-STING positive feedback loop via mitochondrial transfer, which is adjacent to the BLUE and PURPLE streams of the SAMHD1 A565T disease mechanism, but the context is lung adenocarcinoma immunotherapy resistance rather than interferonopathy or SAMHD1 haploinsufficiency.
DOI: 10.1002/advs.202522159

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

The transcription factor IRF8 drives tumor-specific exhaustion in CD8+ T cells. (from Oncology/Tumor Immunology)
Ongaro Marco; Thouenon Romane; Crespo Isaac; Dumez Alexandre; Charmoy Mélanie — 2026
Score: 3/10 | Pathways: JAK-STAT, other

The paper identifies IRF8 as a tumor-specific regulator of CD8+ T cell exhaustion suppressed by sustained IFN-I signaling, which has indirect relevance to the SAMHD1 disease context via the JAK-STAT/IFN-I axis, but does not engage any core pathways (cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, dNTPase) and focuses on tumor immunology rather than interferonopathy, mitochondrial dysfunction, or the family phenotypes described.
DOI: 10.1084/jem.20252115

Pathway Coverage This Week

cGAS-STING: 11 papers
VDAC1: 8 papers
POLG-mtDNA: 7 papers
treatment-target: 7 papers
other: 5 papers
ISG15-mitophagy: 4 papers
NLRP3: 3 papers
clinical-phenotype: 3 papers
JAK-STAT: 2 papers
IRF7-metabolic: 1 papers
mTOR-lysosomal: 1 papers
ME-CFS: 1 papers
AGS-spectrum: 1 papers

June 22, 2026
in Weekly Digest
1 min read

SAMHD1 Research Digest — 2026-06-22

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 0 papers evaluated | 0 high-relevance (≥7) | 0 medium (5–6) | 0 low (3–4) | 0 scored <3

---

Pathway Coverage This Week

June 21, 2026
in Weekly Digest, cGAS-STING, POLG-mtDNA, VDAC1, treatment-target
12 min read

SAMHD1 Research Digest — 2026-06-21

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 27 papers evaluated | 12 high-relevance (≥7) | 9 medium (5–6) | 6 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Nucleotide metabolism reprogramming in obesity-associated cardiovascular inflammation: a new perspective (from Cardiology/Immunometabolism)
Taoming Qian; Mei Zhang; Yuhan Liu; Donghao Guo; Juan Jin — Frontiers in Immunology 2026
Score: 9/10 | Pathways: dNTPase, NLRP3, POLG-mtDNA, VDAC1, urate-NLRP3, treatment-target, clinical-phenotype, other

This paper directly models the SAMHD1→dNTP accumulation→mitochondrial dNTP import (SLC25/PNC transporters)→mtDNA oxidation→NLRP3 hyperactivation axis that is the core PURPLE and GOLD mechanism of the disease profile, demonstrating it in a cardiovascular/macrophage context with therapeutic node identification, making it highly mechanistically relevant even without the specific A565T variant.
DOI: 10.3389/fimmu.2026.1829718

The leaked mitochondrial DNA activated the cGAS-STING signaling pathway and exacerbated the motor dysfunction in mice caused by MPTP. (from Neurology/movement disorders)
Zhu Guangyao; Yu Xuanjie; Guo Yi; Yang Liting; Yang Qianhui — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the BLUE stream mechanism central to the disease model: mitochondrial stress → mtDNA leakage into cytosol → cGAS-STING activation → neuroinflammation, and validates STING inhibition as a therapeutic target, with direct relevance to the SAMHD1/VDAC1-mtDNA escape axis even though SAMHD1 is not mentioned.
DOI: 10.1016/j.expneurol.2026.115876

STING-OPTN signaling confers cytoprotection through TBK1-dependent mitophagy. (from Cell biology / mitochondrial quality control)
Zebo Huang; Jin-Yi Lin; Ling-Jun Cheng; Yong Wu; Xiangzheng Gao — Cell reports 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, mTOR-lysosomal, treatment-target

This paper directly implicates the cGAS-STING pathway as an upstream regulator of mitophagy via TBK1-OPTN signaling, which is mechanistically central to the BLUE and RED streams of the disease model—where constitutive STING activation from VDAC1/mtDNA escape not only drives IFN-I but also perturbs mitochondrial quality control, and the STING-OPTN mitophagy axis disruption switches cells toward apoptosis, directly mirroring the double mitophagy block (ISGylation of MFN1/2 and BECN1) and the apoptosis-autophagy switch (BIK/BH3) predicted in the family's pathomechanism.
DOI: 10.1016/j.celrep.2026.117515

STING1 senses mitochondrial damage to promote mitophagy. (from Cell biology / autophagy)
Zebo Huang; Jin-Yi Lin; Ling-Jun Cheng; H. Tan; Hanming Shen — Autophagy 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, POLG-mtDNA, ME-CFS, treatment-target

This paper directly demonstrates that STING1 acts as a non-canonical upstream regulator of PINK1/Parkin-dependent mitophagy via TBK1-OPTN phosphorylation, revealing a critical mechanistic intersection with the RED and BLUE streams of the disease model: in SAMHD1 haploinsufficiency, chronic cGAS-STING activation would simultaneously drive IFN-I (canonical) and dysregulate mitophagy quality control (non-canonical), and disruption of the STING1-TBK1-OPTN axis shifts cell fate toward apoptosis rather than pro-survival mitophagy, directly explaining the double mitophagy block and accumulation of damaged mitochondria central to the family's interferon-mitochondrial syndrome.
DOI: 10.1080/15548627.2026.2689463

cGAS-STING signaling pathway: a central pathological mechanism and emerging therapeutic target for postoperative cognitive dysfunction. (from Anesthesiology/Perioperative Neuroscience)
Wu Xiaoqin; Zhong Baolin; Xu Yongxing; Lai Yinsiqing; Wen Xinming — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target

This review directly describes the mtDNA-cGAS-STING-neuroinflammation axis with pyroptosis and mitophagy failure as central mechanisms, which maps precisely onto the BLUE and RED streams of the SAMHD1 haploinsufficiency model, and identifies cGAS-STING inhibition and mitophagy promotion as therapeutic targets directly applicable to this disease mechanism.
DOI: 10.1016/j.brainres.2026.150432

Runx1-Snx9 axis drives the pathological secretion of mitochondrial-derived vesicles to activate cGAS-STING signaling in acute pancreatitis. (from Gastroenterology/Pancreatology)
Gao Mengqi; Xiao Guohui; Chen Kunhao; Li Shiyu; Chen Cong — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, other

This paper directly characterizes a novel upstream mechanism (Runx1-Snx9 axis) driving mitochondrial-derived vesicle secretion and mtDNA release that activates macrophage cGAS-STING signaling — the same BLUE stream pathway central to SAMHD1 haploinsufficiency — providing a mechanistic parallel for how cytosolic/extracellular mtDNA fragments trigger chronic interferon activation, even though the context is acute pancreatitis rather than SAMHD1 dysfunction.
DOI: 10.1186/s12951-026-04687-6

Environmental enrichment mitigates sevoflurane-induced neurodevelopmental injury via cGAS-STING-dependent microglial modulation. (from Pediatric anesthesiology/neurodevelopment)
Li Feixiang; Gong Bingqing; Wu Haiyan; Yang Yongyan; Luo Ying — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, ME-CFS, other

This paper directly demonstrates the mitochondrial dysfunction → mtDNA release → cGAS-STING activation → microglial neuroinflammation → synaptic/cognitive impairment axis, which is mechanistically identical to the BLUE stream in the SAMHD1 haploinsufficiency model, and validates mtDNA-driven cGAS-STING as a tractable intervention target in a neurodevelopmental context relevant to the AuDHD phenotype in the proband.
DOI: 10.1186/s13578-026-01610-2

Beyond proteostasis: LONP1 as an immunometabolic checkpoint in health and disease. (from Mitochondrial biology / proteostasis)
Xie Lin; Wu Li-Hong; Ni Xin-Cheng; Zhang Jiang-Nan — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, NLRP3, VDAC1, mTOR-lysosomal, ME-CFS, treatment-target, other

LONP1 directly regulates mtDNA maintenance and its deficiency triggers mtDNA release activating cGAS-STING—the BLUE stream core mechanism in this disease—while also modulating metabolic enzymes relevant to the mitochondrial-inflammatory convergence and SARS-CoV-2 pathogenesis relevant to ME/CFS post-viral trigger, making this a high-value adjacent mechanism with novel treatment implications.
DOI: 10.1016/j.bcp.2026.118170

Mitophagy in Macrophages: A Metabolic Checkpoint in Inflammation-to-Repair Transition in Atherosclerosis. (from Cardiology/atherosclerosis)
Jie Zhou; Hanxiu Liu; Sen Ma; Haoyang Wang; Ni He — Journal of the American Heart Association 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, treatment-target, POLG-mtDNA

This review directly covers the RED and BLUE stream mechanisms—PINK1/Parkin mitophagy block, mtDNA release activating cGAS-STING and NLRP3 inflammasome in macrophages—with therapeutic targets (metformin, resveratrol, MCC950-analogous NLRP3 inhibition) that map precisely onto the ISG15-mitophagy double-block and VDAC1-cGAS-STING axes central to the SAMHD1 haploinsufficiency syndrome, though SAMHD1 itself is not mentioned.
DOI: 10.1161/jaha.125.048103

The COX2-PGE2-PKA Axis Suppresses Antiviral Immunity by Inhibiting mtDNA-Dependent STING Activation (from Virology/innate immunity (HSV-1 infection model))
P. Vo; Julien Cicero; Zichen Wang; Hiroyuki Hakozaki; Thomas S. Hoang — bioRxiv 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, ISG15-mitophagy, ME-CFS, treatment-target

This paper directly addresses the mtDNA-cytosol-cGAS-STING-IFN-I axis (BLUE stream) and mitophagy regulation thereof, revealing that COX2/PGE2/PKA/STOML2 suppresses STING activation by clearing immunostimulatory cytosolic mtDNA via mitophagy—a regulatory circuit highly relevant because in SAMHD1 haploinsufficiency the mtDNA-cGAS-STING pathway is constitutively overactivated and the ISG15/MFN1/MFN2 mitophagy block prevents this clearance, making COX2/PGE2/PKA axis modulation a potential therapeutic lever.
DOI: 10.64898/2026.04.03.716411

Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis (from Cardiology/Vascular biology)
Hao Liu; Shuai Zhao; Huiqin Gao; Yue Wang; Junyan Gao — Precision Clinical Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, JAK-STAT, POLG-mtDNA, treatment-target

This review directly covers the core convergent mechanism of the disease profile—mt-DAMPs (including mtDNA escape via mitochondrial membrane permeability changes analogous to VDAC1 macropore opening) activating cGAS-STING to drive type I interferon production and NLRP3-mediated IL-1β release—while also detailing the PINK1-Parkin mitophagy pathway that is blocked by ISGylation of MFN1/MFN2 in the RED stream, providing mechanistic depth and atherosclerosis-relevant treatment targets applicable to the interferonopathy-mitochondrial syndrome.
DOI: 10.1093/pcmedi/pbag010

Cytosolic Immunostimulatory DNA Ligands and DNA Damage Activate the Integrated Stress Response, Stress Granule Formation, and Cytokine Production (from Cancer immunotherapy / DNA damage biology)
Trupti Devale; Lekhana Katuri; Gauri Mishra; Aditya Acharya; Praveen Manivannan — Cells 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, ME-CFS, treatment-target, other

This paper directly characterizes the STING-PERK-G3BP1 signaling axis linking cytosolic dsDNA sensing (including mtDNA escape, the core BLUE pathway) to the integrated stress response, stress granule formation, and IFN-I/cytokine production — mechanisms directly downstream of SAMHD1 haploinsufficiency-driven dNTP pool expansion and VDAC1-mediated mtDNA release, and identifies PERK as a novel druggable node that could modulate the chronic interferonopathy in this family.
DOI: 10.3390/cells15020139

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Restoring BECN1-Mediated Autophagy Mitigates Acute Lung Injury Caused by Zinc Oxide Nanoparticles. (from Pulmonary toxicology/nanotoxicology)
Lejiao Mao; Meiling Tan; Xuejun Jiang; Jun Zhang; Ge Xu — Free radical biology & medicine 2026
Score: 6/10 | Pathways: ISG15-mitophagy, NLRP3, mTOR-lysosomal, treatment-target

This paper directly demonstrates that BECN1 haploinsufficiency (heterozygous knockout) impairs mitophagy flux causing accumulation of dysfunctional mitochondria, ROS, and inflammatory cascades—mechanistically parallel to the RED stream where ISGylation of BECN1 blocks autophagy flux in the SAMHD1 disease model, and validates Tat-Beclin1 as a pharmacological rescue strategy for BECN1-dependent mitophagy failure.
DOI: 10.1016/j.freeradbiomed.2026.05.317

Immunoglobulin G complexes from post-infectious ME/CFS, including post-COVID ME/CFS disrupt cellular energetics and alter inflammatory marker secretion (from Neuroimmunology/autoimmunity)
Zheng Liu; Claudia Hollmann; S. Kalanidhi; S. Lamer; Andreas Schlosser — Brain, Behavior, & Immunity - Health 2026
Score: 6/10 | Pathways: ME-CFS, VDAC1, ISG15-mitophagy, JAK-STAT, clinical-phenotype, other

This paper directly characterizes ME/CFS (including post-COVID ME/CFS) IgG-mediated mitochondrial fragmentation and energetic disruption in endothelial cells, providing mechanistic autoimmune context for the proband's post-viral ME/CFS phenotype, with mitochondrial fragmentation highly relevant to the ISG15-MFN1/2 mitophagy block and VDAC1 macropore streams in the disease model.
DOI: 10.1016/j.bbih.2026.101187

Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing (from DNA damage response / genome stability)
Samira Kemiha; Lorena Rejón-Franco; Estelle Ghibaudo; R. Eloiflin; Morgane Chema — The Journal of Biological Chemistry 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, ME-CFS, other

This paper demonstrates that cytoplasmic ISD (the same stimulus generated by VDAC1-mediated mtDNA escape in the BLUE stream) co-activates ATM and DNA-PK damage response kinases independently of cGAS-STING, revealing a parallel DDR arm that could amplify genomic instability and checkpoint activation in SAMHD1 haploinsufficiency where chronic cytosolic dsDNA (from ox-mtDNA fragments) is present.
DOI: 10.1016/j.jbc.2026.111362

African swine fever virus pE199L, as a mitophagy receptor, suppresses antiviral innate immunity to promote viral replication. (from Veterinary virology / ASFV vaccinology)
Xiaoxuan Li; Binbin Ren; Danyang Zhang; Miao Dan; Dongying Liu — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, ME-CFS, other

This paper directly addresses the cGAS-STING pathway and PINK1/Parkin-dependent mitophagy as targets of viral immune evasion—mechanisms central to the SAMHD1 A565T syndrome—demonstrating that mitophagic clearance of TBK1 suppresses type I interferon production, which is the inverse of the constitutive IFN-I overactivation and mitophagy block seen in this family, providing mechanistic insight into how mitophagy flux regulation gates cGAS-STING-IFN-I signaling amplitude.
DOI: 10.1080/15548627.2026.2654982

B33-01 Cisd1 Regulates the Sting Pathway Through the Ubiquitin-proteasome System to Ameliorate COPD Progression (from Pulmonology/COPD)
J. Gao; Y. Song — American Journal of Respiratory and Critical Care Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, other

This paper describes a mitochondria-to-STING innate immunity axis where CISD1 (a mitochondrial iron-sulfur protein) regulates STING degradation via K48-ubiquitination through Ubr5, directly engaging the cGAS-STING-TBK1-IRF3 pathway that is a core loop (BLUE) in the SAMHD1 haploinsufficiency mechanism, offering a novel STING regulatory checkpoint (ubiquitin-proteasome degradation) relevant to modulating the chronic interferon signature seen in the family, though SAMHD1 and dNTP biology are not addressed.
DOI: 10.1093/ajrccm/aamag162.1786

Toward a Molecular Reclassification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Integrating Multi-Omics, Machine Learning, and Precision Medicine (from Computational biology / precision medicine / multi-omics)
Joshua Frank; Nicole Nesterovitch; Chetana Movva; N. Klimas; L. Nathanson — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: ME-CFS, JAK-STAT, POLG-mtDNA, cGAS-STING, NLRP3, ISG15-mitophagy, treatment-target, other

This review directly addresses ME/CFS molecular reclassification and identifies chronic innate immune activation, mitochondrial dysfunction, and genetic risk variants as core pathophysiology—all of which map onto the SAMHD1 A565T interferon-mitochondrial syndrome mechanism—but does not specifically implicate SAMHD1, cGAS-STING, or the dNTPase axis, making it a high-quality contextual reference for the proband's ME/CFS phenotype rather than a mechanistic confirmation.
DOI: 10.3390/ijms27104436

Ca2+-driven self-amplified nanoplatform targeting ER-mitochondrial calcium crosstalk for synergistic apoptosis induction and tumor immune microenvironment remodeling (from Oncology/nanomedicine)
Yucui Ding; Xinyu Liu; Jianlong Fu; Jianyue Xue; Xueni Fan — Materials Today Bio 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, NLRP3, other

The paper directly engages the IP3R-GRP75-VDAC complex, mitochondrial permeability transition, and Mn2+-driven cGAS-STING activation—all mechanistically overlapping with the BLUE and PURPLE streams of the SAMHD1 interferonopathy model—but in an oncology/nanomedicine context with no connection to SAMHD1 haploinsufficiency, dNTP pool dysregulation, or the family's clinical phenotypes.
DOI: 10.1016/j.mtbio.2026.103339

Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics (from Virology/Retrovirology)
K. D. Perera; E. Oltra; S. Carding — International Journal of Molecular Sciences 2026
Score: 5/10 | Pathways: ME-CFS, cGAS-STING, JAK-STAT, AGS-spectrum, other

The paper addresses ME/CFS pathogenesis through HERV-driven innate immune activation (including cGAS-STING sensing, LTR-driven interferon amplification, and JAK-STAT signaling) which overlaps mechanistically with the IFN-I loop central to SAMHD1 haploinsufficiency syndrome, and HERV reactivation is plausibly potentiated by the dNTP pool expansion that SAMHD1 normally suppresses (since SAMHD1 restricts retrotransposon/HERV reverse transcription), but the paper does not address SAMHD1, VDAC1, NLRP3, mitochondrial pathways, or ISG15-mitophagy directly.
DOI: 10.3390/ijms27104309

Dual-targeting macrophage membrane nanosystem enhances radiotherapy-induced antitumor immunity via synergistic nuclear and mitochondrial DNA damage. (from Oncology/Nanomedicine)
Guangyu Ju; Qi Ding; Hongcang Gu; Rao Liu; Xiao Liu — Biomaterials science 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, other

This paper demonstrates that mitochondrial membrane permeabilization (analogous to VDAC1 macropore opening in the BLUE stream) causes cytosolic accumulation of mitochondrial nucleic acids activating innate immune signaling and type I interferon, which mechanistically parallels the SAMHD1/VDAC1-mtDNA-cGAS-STING axis, but the context is engineered radiotherapy enhancement in glioma with no SAMHD1 involvement.
DOI: 10.1039/d6bm00279j

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

TFEB-mediated autophagy dysregulation links with PRPF31 deficiency-induced photoreceptor death via PLK4 downregulation. (from Ophthalmology/retinal genetics)
Lujia Zhang; Yuntao Qu; S. Yao; Luying Han; Guangming Liu — Experimental eye research 2026
Score: 4/10 | Pathways: mTOR-lysosomal, other

This paper describes a haploinsufficiency-driven autophagic hyperactivation and mitochondrial dysfunction cascade (PLK4-TFEB axis) that shares conceptual overlap with the lysosomal/autophagy failure and mitochondrial damage themes in the SAMHD1 syndrome, but involves entirely different genes (PRPF31, PLK4, TFEB) in a retinal degeneration context with no connection to interferon signaling, dNTP metabolism, cGAS-STING, or any other core SAMHD1 pathway.
DOI: 10.1016/j.exer.2026.111000

C-terminal tail of MAVS dictates organelle targeting and innate immune response (from Cell biology / virology)
Terence Lee; Kiki Cham; Dong-Yan Jin — Cell Communication and Signaling : CCS 2026
Score: 4/10 | Pathways: cGAS-STING, other

MAVS organelle-specific signaling is upstream of IRF3/IFN-β activation (a convergent endpoint in the BLUE stream), but this paper addresses RNA sensing via RIG-I-like receptors rather than the cGAS-STING/VDAC1-mtDNA axis central to SAMHD1 haploinsufficiency, making the connection tangential despite sharing IRF3 and type I interferon as readouts.
DOI: 10.1186/s12964-026-02753-y

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation. (from Virology/RNA biology)
Djamal Brahim Belhaouari; Anil Pant; Santiago Navarro-Forero; Fernando Cantu; Zh — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 4/10 | Pathways: POLG-mtDNA, ME-CFS, other

This paper reveals an interferon-independent mechanism by which RNA accumulation directly impairs mitochondrial membrane potential and respiration, which is tangentially relevant as the SAMHD1 haploinsufficiency model involves mitochondrial dysfunction, but the paper's core mechanism (excess RNA perturbing mitochondria during poxvirus infection) is not a primary pathway in the SAMHD1 A565T disease model and involves no direct overlap with cGAS-STING, VDAC1, ISG15, NLRP3, or dNTPase axes.
DOI: 10.1073/pnas.2605194123

Genetic and transcriptomic signatures of host control in HIV-1 infection. (from Infectious disease / virology)
Oreshkov Sergey; Thorball Christian W; Meylan Jenny; Muriset Maude; Calmy Alexan — 2026
Score: 3/10 | Pathways: dNTPase, other

This paper identifies SAMHD1 as an HIV-1 restriction factor counteracted by Vpx in passing, but focuses on transcriptomic correlates of HIV load control rather than SAMHD1 dNTPase function, haploinsufficiency, or the cGAS-STING/interferonopathy/mitochondrial pathways central to the disease profile.
DOI: 10.1186/s12977-026-00679-4

Degradable STING nanomodulators orchestrate the innate-to-adaptive immune response for NIR-II photothermal-immunotherapy via a cancer-immunity cycle (from Nanomedicine/oncology)
Qiaolin Wei; Zirui Zhu; Yue Li; Siying Sun; Ge Gao — Materials Today Bio 2026
Score: 3/10 | Pathways: cGAS-STING, other

While this paper involves cGAS-STING pathway activation, it does so in the context of engineered cancer nanoparticle immunotherapy using exogenous Zn2+/ROS/photothermal stimulation in solid tumors, with no mechanistic relevance to SAMHD1 haploinsufficiency, endogenous dNTP pool dysregulation, interferonopathy, or any of the family's clinical phenotypes.
DOI: 10.1016/j.mtbio.2026.103028

Bispecific Macrophage Nano-Engager Couples Dual Checkpoint Blockade with Stimulator of Interferon Genes Activation to Potentiate Antitumor Immunity. (from Oncology/Nanomedicine)
Bao-Toan Dang; Khang-Yen Pham; Huyen T. Le; Thoa Thi Kim Nguyen; A. T. Vu — ACS nano 2026
Score: 3/10 | Pathways: cGAS-STING, JAK-STAT, other

This paper activates STING pharmacologically (SR717 agonist) in a tumor immunotherapy context, which is mechanistically opposite to the disease profile where cGAS-STING is pathologically overactivated by cytosolic mtDNA fragments; the paper's engagement with STING/IFN pathways is incidental to its oncology focus and offers no direct mechanistic insight into SAMHD1 haploinsufficiency or the interferonopathy cascade.
DOI: 10.1021/acsnano.6c01144

Pathway Coverage This Week

cGAS-STING: 21 papers
other: 20 papers
POLG-mtDNA: 15 papers
VDAC1: 12 papers
treatment-target: 12 papers
ME-CFS: 11 papers
ISG15-mitophagy: 10 papers
NLRP3: 9 papers
JAK-STAT: 8 papers
mTOR-lysosomal: 4 papers
dNTPase: 2 papers
clinical-phenotype: 2 papers
urate-NLRP3: 1 papers
AGS-spectrum: 1 papers

June 14, 2026
in Weekly Digest, cGAS-STING, NLRP3, POLG-mtDNA, VDAC1
17 min read

SAMHD1 Research Digest — 2026-06-14

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 41 papers evaluated | 12 high-relevance (≥7) | 17 medium (5–6) | 12 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential. (from Ophthalmology (senior author Liu Zuguo is an ophthalmologist, suggesting ocular surface/corneal innate immunity application))
Yan Dan; Hu Jiaoyue; Liu Zuguo; Ouyang Weijie — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, JAK-STAT, NLRP3, POLG-mtDNA, treatment-target, AGS-spectrum, ME-CFS

This comprehensive review directly covers the BLUE stream (cGAS→cGAMP→STING→IRF3→IFN-I) that is central to the SAMHD1 A565T mechanism, including mitochondrial/micronuclear DNA sensing, liquid-liquid phase separation dynamics, metabolic-immune crosstalk, neurodegenerative and autoimmune contexts, and emerging small-molecule inhibitors (including cGAS inhibitors like IMSB301-class compounds) that represent direct therapeutic targets for this interferonopathy.
DOI: 10.1186/s43556-026-00478-5

Mitochondria as convergence hubs for innate immunity pathways. (from Cell biology / mitochondrial biology)
Guo Yunhao; Xue Yansong — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other

This review directly addresses the convergence of mitochondria as innate immune signaling hubs integrating cGAS-STING, NLRP3, and MAVS pathways through mitochondrial DAMPs—precisely the mechanistic framework (BLUE, PURPLE, RED streams) underlying the SAMHD1 A565T interferonopathy, linking mitochondrial dysfunction to autoimmunity and offering therapeutic pathway insights.
DOI: 10.1038/s42003-026-10479-3

Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis. (from Neurology/Neuroimmunology)
Liu Yongqing; Ye Yingzhi; Fan Minghua; Cheng Henry Yi; Sun Shuying — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, treatment-target, other

This paper directly demonstrates the mechanistic axis of cytosolic mtDNA release → cGAS-STING → NLRP3 chronic neuroinflammation in microglia, and critically implicates Cmpk2 (a mitochondrial dNTP kinase regulating mtDNA synthesis) as a regulatory node—directly paralleling SAMHD1's role in dNTP pool control and mtDNA-driven innate immune activation in the BLUE and PURPLE pathways, with KAT7 inhibition as a pharmacologically tractable intervention point.
DOI: 10.1016/j.neuron.2026.05.015

A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation. (from Structural biology / mitochondrial biophysics)
De Pinto Vito; Battiato Giuseppe; Conti-Nibali Stefano; Cubisino Salvatore Anton — 2026
Score: 8/10 | Pathways: VDAC1, cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, ISG15-mitophagy

This review directly covers VDAC1 oligomerization, macropore formation, mtDNA escape mechanisms, outer mitochondrial membrane permeabilization, and emerging small-molecule modulators (including VBIT-4 class compounds), all of which are central to the BLUE stream (SAMHD1/VDAC1 interaction loss → VDAC1 macropore → cytosolic mtDNA → cGAS-STING-IRF3-IFN-I) in the disease mechanism, and discusses therapeutic targeting strategies directly applicable to this interferonopathy.
DOI: 10.1042/bst20250480

Mitochondrial kinase CMPK2 in immune homeostasis and disease: from metabolic regulation to inflammatory signaling. (from Biochemistry/Virology)
Junhu Yao; Mengjie Shi; Siyan Chen; Huan Zhang; Yiming Lin — International immunopharmacology 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, ME-CFS, treatment-target, other

CMPK2 is a mitochondrial nucleotide kinase that directly links mitochondrial dNTP pool regulation (UTP/CTP synthesis for mtDNA replication) to both NLRP3 inflammasome activation and cGAS-STING signaling via oxidized/escaped mtDNA, positioning it as a mechanistic neighbor to SAMHD1's dNTPase deficiency cascade, with additional relevance to SARS-CoV-2/post-viral contexts and SLE interferonopathy overlapping the AGS spectrum.
DOI: 10.1016/j.intimp.2026.116582

MitoSafe hypothesis: safeguarding mitochondrial morphology and innate immunity. (from Cell biology / mitochondrial biology)
Nora Haggerty; Kentaro Nakamura; H. Sesaki; M. Iijima — Trends in cell biology 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, ME-CFS

This paper directly addresses PINK1/Parkin-mediated mitophagy dysregulation leading to mitochondrial enlargement, mtDNA release, and STING-mediated inflammation — precisely the RED and BLUE pathway loops in the SAMHD1 haploinsufficiency mechanism where ISGylation of MFN1/MFN2 blocks PINK1/Parkin mitophagy, causing damaged mitochondrial accumulation, mtDNA escape, and cGAS-STING activation.
DOI: 10.1016/j.tcb.2026.04.007

Neuroprotection by lactate in Parkinson's disease: A novel anti-inflammatory mechanism via 14-3-3 protein lactylation. (from Neurology/Neurodegeneration (Parkinson's disease))
Zhang Qi; Liu Ming; Cao Wen-Jing; Zou Wei; Zhang Ping — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the mechanistic triad central to SAMHD1 haploinsufficiency pathology—NLRP3 inflammasome activation, cytosolic mtDNA release, and cGAS-STING pathway engagement—and shows that lactate/14-3-3 lactylation can interrupt this loop at multiple nodes (NLRP3 suppression → reduced GSDMD-driven mitochondrial injury → decreased cytosolic mtDNA → attenuated cGAS-STING), identifying lactate signaling as a novel upstream brake on the BLUE and PURPLE pathway convergence points relevant to the disease mechanism.
DOI: 10.1016/j.bbadis.2026.168314

A Narrative Review of the mtDNA-Stimulated Inflammatory Axis in Sepsis-Induced Acute Lung Injury: Cellular Mechanisms and Therapeutic Targeting. (from Critical care / pulmonology)
Ma Shuqi; Pan Qiusha; Zeng Ruifeng; Liu Quanle; Yang Suyi — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other

This review directly covers the mtDNA-cGAS-STING-NLRP3 inflammatory axis with cell-type-specific mechanistic detail and therapeutic targeting strategies (STING inhibitors, MCC950-class NLRP3 blockers) that map precisely onto the BLUE and PURPLE pathways of SAMHD1 haploinsufficiency, where cytosolic mtDNA escape via VDAC1 macropores drives chronic interferonopathy and pyroptosis, making it highly mechanistically relevant even though SAMHD1 is not mentioned.
DOI: 10.1093/jleuko/qiag077

Small but mighty: mitochondrial DNA at the centre of retrograde signalling (from Cell biology / mitochondrial biology)
Eve Harding; Veronica Bazzani; C. Vascotto — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, dNTPase, ME-CFS, other

This review directly addresses mtDNA escape, retrograde signalling via cGAS-STING innate immune activation, POLG/mtDNA instability, and mitochondrial dynamics—all core mechanistic streams of the SAMHD1 A565T syndrome—making it highly relevant as a mechanistic framework paper despite lacking direct SAMHD1 data.
DOI: 10.1186/s12964-026-02858-4

Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies (from hepatology/transplant surgery)
Ruotong Shen; Peng An; Meng Chen; Ping Lu; Jingjing Yang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other

This paper directly elaborates the mtDNA-release → cGAS-STING → NLRP3 inflammasome → pyroptosis vicious cycle that constitutes the BLUE and PURPLE mechanistic streams of the SAMHD1 haploinsufficiency syndrome, covering VDAC1 permeability, mitophagy failure, and pharmacological intervention points (cGAS-STING and NLRP3 inhibition) directly relevant to therapeutic targeting in the family's interferonopathy.
DOI: 10.1186/s12967-026-08155-5

From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases (from Evolutionary biology / mitochondrial biology)
Weilong Hong; Shiyu Long; M. Ashrafizadeh; Gautam Sethi; Chenyang Duan — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other

This review directly addresses the core convergence of mitochondrial dysfunction, mtDNA release, DAMP-driven innate immune activation (cGAS-STING, NLRP3), and mitophagy failure that constitutes the mechanistic heart of the SAMHD1 A565T interferonopathy model, including VDAC1-mediated mtDNA escape and the progression from mitochondrial stress to systemic inflammatory amplification, though SAMHD1 itself is not mentioned.
DOI: 10.1186/s12964-026-02736-z

Understanding cardiovascular aging as a disorder of mitochondrial network (from Cardiology)
Taslima Akter Shila; Dhrubo Ahmad; Jianli Zhao; Huilan Tan; Bo Wang — The Journal of Cardiovascular Aging 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, POLG-mtDNA, NLRP3, treatment-target, clinical-phenotype

This review directly covers mtDNA release activating cGAS-STING, mitophagy/fission-fusion defects, and mitochondrial network dysfunction driving sterile inflammation — all core RED/BLUE/PURPLE stream mechanisms in the SAMHD1 haploinsufficiency model — with cardiovascular aging implications relevant to the family's interferonopathy-cardiac phenotype risk.
DOI: 10.20517/jca.2026.07

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles. (from Geroscience/aging biology)
Xiang Zijie; Chen Yu; Liu Xishui; Lu Haowen; Yang Yuqing — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, mTOR-lysosomal, treatment-target, other

This review systematically covers mitochondrial dysfunction mechanisms directly relevant to the disease model—including cGAS-STING activation by escaped mtDNA, mitophagy failure, mitochondrial dynamics (MFN1/MFN2-related), biogenesis (PGC-1alpha), and mtDNA instability—and surveys therapeutic strategies (including mitochondrial transplantation and base editing) that could apply to SAMHD1 haploinsufficiency's convergent interferon-mitochondrial syndrome, though it does not address SAMHD1 specifically.
DOI: 10.1002/mco2.70790

Intrinsically Mitochondria-Targeting Nanozyme via Coordination-Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia-Reperfusion Injury. (from Nanomedicine/Neurology)
Zheng Wenxuan; Wang Zhicheng; Zhou Xin; Wang Shuya; Shi Xiaojing — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the mtDNA leakage → cGAS-STING neuroinflammatory axis (core BLUE stream) and shows that stabilizing mitochondrial outer membrane proteins (including VDAC1-related outer membrane targets) prevents mtDNA escape, offering mechanistic and therapeutic parallels to the SAMHD1 haploinsufficiency syndrome's central pathogenic loop, though it is framed in cerebral ischemia-reperfusion rather than interferonopathy or SAMHD1 contexts.
DOI: 10.1002/advs.76038

Size-dependent ruthenium/ceria nanozymes synchronize catalytic ROS scavenging and electrostatic mtDNA sequestration for periodontitis therapy. (from Dental/biomaterials nanomedicine)
Zhang Fanrou; Qi Manlin; Liu Jia; Du Juanrui; Shi Fangyu — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NLRP3, treatment-target, other

This paper directly addresses the mtDNA escape → cytosolic mtDNA → innate immune activation axis (core BLUE pathway) and mitochondrial oxidative stress, proposing electrostatic sequestration of cytosolic mtDNA as a therapeutic strategy that could conceptually apply to SAMHD1-driven cGAS-STING activation, though it is disease-specific to periodontitis and not mechanistically linked to SAMHD1 or dNTPase dysfunction.
DOI: 10.1186/s12951-026-04660-3

Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease. (from Endocrinology/reproductive biology)
Bynum Hanna; Edwards Kristin S — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, JAK-STAT, ME-CFS, treatment-target, pregnancy-fetal, other

This review directly covers mtDNA release activating cGAS-STING, NLRP3 inflammasome, and mitochondrial quality control pathways central to the SAMHD1 A565T mechanism, and addresses sex-hormone modulation of mitochondrial biogenesis, ROS, and immunometabolic signaling that would modulate disease expression across the multi-generational family, but does not address SAMHD1 specifically or dNTP pool dynamics.
DOI: 10.3390/ijms27114966

No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases (from Mitochondrial disease / clinical genetics)
M. Marchais; Alessandra Pennisi; Alexandre Pierga; A. Lepelley; Nicolas Cagnard — European Journal of Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, ME-CFS, other

This paper directly interrogates the cGAS-STING axis and cytosolic mtDNA leakage in patient fibroblasts with mitochondrial disease, finding that ISG elevation and mtDNA escape are dissociated—a critical negative finding that complicates the BLUE/PURPLE pathway model where VDAC1-mediated mtDNA escape drives IFN-I in SAMHD1 haploinsufficiency, and raises important methodological cautions about using fibroblast models to validate the proposed SAMHD1 A565T interferon-mitochondrial mechanism.
DOI: 10.1002/eji.70176

Advances in Elucidating the Mitochondrial DNA Mechanisms Underlying Ozone-Induced Inflammation (from Environmental toxicology/pulmonology)
Qian Chen; Hao Liu; Junhe Zhou; Yongjie Wei; Lingyan He — Toxics 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ME-CFS, other

This review directly addresses mtDNA escape from dysfunctional mitochondria as a DAMP activating innate immune/inflammatory pathways (cGAS-STING, NLRP3), which mirrors the BLUE and PURPLE mechanistic streams of SAMHD1 haploinsufficiency, though the upstream trigger is ozone rather than dNTP pool expansion via SAMHD1 loss.
DOI: 10.3390/toxics14030248

Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects (from Cardiology)
Mingyang Ni; Aijia Zheng; Hang Zheng; Wenqing Jia; Yuansheng Wang — Frontiers in Cardiovascular Medicine 2026
Score: 6/10 | Pathways: POLG-mtDNA, cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, clinical-phenotype, other

This review directly addresses mtDNA mutation-driven innate immune activation (cGAS-STING, NLRP3), mitochondrial structural dysfunction (VDAC1, dynamics), oxidative stress, and metabolic reprogramming in cardiac disease — all core loops of the SAMHD1 interferonopathy mechanism — with cardiology phenotype relevance given the family's interferonopathy-driven mitochondrial cardiomyopathy risk, though SAMHD1 itself is not mentioned.
DOI: 10.3389/fcvm.2026.1781927

Lethal effects of a hyperactive dGTP triphosphohydrolase in E. coli. (from microbiology/biochemistry)
Bhawsinghka Niketa; Glenn Katie F; Klemm Bradley P; Singh Deepa; Day Ryan C — 2026
Score: 5/10 | Pathways: dNTPase, POLG-mtDNA, other

This paper directly investigates the consequences of hyperactive dGTPase activity causing dGTP depletion and chromosomal disruption in E. coli, which is mechanistically inverse but conceptually adjacent to the SAMHD1 haploinsufficiency disease model where reduced dNTPase activity causes dGTP pool expansion — both scenarios underscore the critical importance of precise dNTP pool regulation, particularly dGTP, for genomic integrity and cell viability.
DOI: 10.1093/genetics/iyag139

Mitochondrial Metabolic Reprogramming in Colorectal Cancer-Associated Fibroblasts: An Up-to-Date Review. (from Oncology/Cancer Biology)
Li Ying; Chanda Dipanjan; Jeon Seong-Woo; Jeon Jae-Han; Kim Min-Ji — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, mTOR-lysosomal, other

This review covers CAF mitochondrial reprogramming in CRC and explicitly discusses mtDNA-mediated cGAS-STING signaling, AMPK-PGC-1α, mitophagy/fission-fusion dynamics, and ROS-NF-κB pathways that are directly mechanistically relevant to the SAMHD1 interferonopathy model, but the context is tumor-stroma crosstalk rather than germline interferonopathy or dNTPase haploinsufficiency, making the connection indirect.
DOI: 10.3390/cancers18111786

Manganese Vacancy-Engineered Prussian Blue Triggers Pyroptosis-Driven Innate Immunity for Second Near-Infrared Region Photoimmunotherapy. (from Oncology/Nanomedicine)
Wang Xiaorui; Li Runtao; Wang Ye; Li Yunpeng; Liu Liren — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, other

This paper demonstrates the mechanistic link between ROS-induced gasdermin E-mediated pyroptosis, cytosolic mtDNA release, and cGAS-STING activation—pathways directly relevant to the SAMHD1 disease model—but in an engineered oncology/photoimmunotherapy context that is mechanistically informative but clinically distant from haploinsufficiency-driven interferonopathy.
DOI: 10.1021/acsnano.6c05567

Barrier-to-autointegration factor protects against the cGAS-STING response to chromatin bridges. (from Cell biology / mitosis)
Chastant Laura; Normandin Karine; El-Mortada Firas; Servant Marc J; Archambault * — 2026
Score: 5/10* | Pathways: cGAS-STING, other

This paper characterizes BAF (Barrier-to-Autointegration Factor) as a suppressor of cGAS-STING activation via chromatin bridge stabilization—a nuclear/mitotic mechanism distinct from the SAMHD1/VDAC1/mtDNA route, but confirming that cGAS-STING can be potently activated by aberrant chromatin structures and that IRF3-dependent proinflammatory transcription results; relevant as contextual mechanistic background for the BLUE stream but does not touch SAMHD1, mitochondria, dNTP pools, or any family phenotype directly.
DOI: 10.1371/journal.pgen.1012191

Acacetin ameliorates MASLD by inhibiting the Notch1 pathway in hepatocytes and reprogramming macrophage polarization via Keap1-Nrf2-mediated restraint of ferroptosis. (from Hepatology)
Xu Jun; Ying Huiya; Wang Yixiao; Zeng Yuan; Zhao Qian — 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, IRF7-metabolic, NLRP3, treatment-target, other

The paper directly demonstrates that mitochondrial injury drives mtDNA release activating cGAS-STING in macrophages (a core BLUE-stream pathway in the disease model), and documents hepatic steatosis/MASLD — a tracked family phenotype — but the mechanism is studied in a non-SAMHD1 context with no connection to dNTPase haploinsufficiency, making it an adjacent mechanistic parallel rather than a direct hit.
DOI: 10.1016/j.metabol.2026.156670

Mitochondrial OXPHOS restricts SARS-CoV-2 replication. (from virology/cell metabolism)
Soto Albrecht Yentli E; Morrow Ryan M; Kenney Devin; Olali Arnold Z; Wacquiez Al — 2026
Score: 5/10 | Pathways: POLG-mtDNA, ME-CFS, dNTPase, other

This paper demonstrates that mitochondrial OXPHOS suppresses SARS-CoV-2 replication via metabolic balance rather than innate immune differences, which is indirectly relevant because the SAMHD1 A565T haploinsufficiency causes mitochondrial dysfunction (via POLG stalling, perturbed dNTP pools, and OXPHOS impairment), potentially creating a permissive environment for enhanced SARS-CoV-2 replication and post-viral ME/CFS triggering in the proband, but the paper explicitly rules out innate immune pathway differences as the mechanism, limiting its direct relevance to the cGAS-STING/interferonopathy axis central to this disease.
DOI: 10.1126/sciadv.adz3081

Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion (from Oncology)
Fan Yang; Rui Liu; Li Liu; Aijie Zhang; Bo Li — Frontiers in Immunology 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, other

This review covers cGAS-STING, type I interferon, and innate immune evasion mechanisms directly relevant to the SAMHD1 interferonopathy framework, including metabolic reprogramming and ubiquitin-mediated regulation, but the lung cancer focus and lack of SAMHD1, NLRP3, VDAC1, or mitophagy content limits direct applicability to the disease profile.
DOI: 10.3389/fimmu.2026.1842558

The human cytomegalovirus vMIA protein inhibits apoptosis and innate immune signaling in human Mueller cells. (from ophthalmology/virology)
M. M. Sauter; H. Noel; Curtis R. Brandt — Experimental eye research 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, ME-CFS, other

The paper demonstrates viral modulation of the cGAS-STING pathway and mitochondrial apoptosis signaling via vMIA, which intersects with core BLUE-stream mechanisms (cGAS-STING, mitochondrial morphology/MAVS, VDAC1-adjacent apoptosis) relevant to SAMHD1 interferonopathy, but the retinal/ocular context and viral immunoevasion framing are tangential to the family's haploinsufficiency syndrome.
DOI: 10.1016/j.exer.2026.111009

JAK inhibition in PD-1 immunotherapy and tumor microenvironment (from Oncology/Immuno-oncology)
Ziyuan Liu; Jiaqi Liu; Hongyu Chu; Zhuming Lu; Shengshan Xu — Frontiers in Immunology 2026
Score: 5/10 | Pathways: JAK-STAT, treatment-target, other

This review covers JAK/STAT signaling and JAK inhibitors (baricitinib, ruxolitinib class) in the tumor microenvironment, which are directly relevant as treatment targets for the SAMHD1 interferonopathy (IFN-I → JAK-STAT1/2 → ISG15 → mitophagy block), but the paper's focus is on cancer immunotherapy resistance rather than the interferonopathy or mitochondrial mechanisms central to SAMHD1 haploinsufficiency, making it an indirect therapeutic connection.
DOI: 10.3389/fimmu.2026.1790936

Dysregulated dsRNA sensor signaling and viral infection during onset of pediatric autoimmune interferonopathy (from Pediatric rheumatology/myology)
MOREAU, T. R.; AQUINO, Y.; ZHU, Y. Y.; BONDET, V.; ALBERT-VEGA, C.; DONNADIEU, F — bioRxiv (preprint) 2026
Score: 5/10 | Pathways: JAK-STAT, AGS-spectrum, ME-CFS, cGAS-STING, clinical-phenotype, other

This paper demonstrates SARS-CoV-2 and RNA viral triggers driving dysregulated IFN-I/MDA5 signaling with myeloid ISG enrichment in pediatric autoimmune interferonopathy (JDM), which is mechanistically adjacent to the SAMHD1 haploinsufficiency model—particularly the viral trigger hypothesis (proband's adenovirus/SARS-CoV-2 onset), IFN-I loop amplification, and JAK-STAT pathway dysregulation—but does not address SAMHD1, cGAS-STING, VDAC1, mtDNA, or the specific dNTP-driven mechanism.
DOI: 10.64898/2026.05.27.728148

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases. (from cell biology / molecular pharmacology)
Borlepawar Ankush; Neu Marco; Ma Ziqi; Deshpande Anushka; Bühringer Hannah — 2026
Score: 4/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, NLRP3, other

This broad proteostasis review tangentially touches autophagy-mitophagy, ubiquitin-proteasome, and lysosomal pathways relevant to the ISG15-mitophagy block and NLRP3 inflammasome axes in the disease model, but contains no specific focus on SAMHD1, cGAS-STING, interferonopathy, or the core molecular players driving the convergent interferon-mitochondrial syndrome.
DOI: 10.1038/s41392-026-02714-4

Association Between Type I Interferonopathies and the Development of Cutaneous Sarcoidosis, Morphea, Lichen Planus and Granuloma Annulare: A Retrospective Cohort Study. (from Dermatology)
Block Brandon; Mehta Jaanvi; Soto-Canetti Gabriela; Tang Alice; Spingler Riley — 2026
Score: 4/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, other

This paper documents clinical associations between IFN-I-driven systemic diseases and specific autoimmune dermatoses (LP, morphea, CS, GA), confirming that chronic type I interferonopathy states predispose to these skin conditions, which is peripherally relevant as downstream phenotypic consequences of the same JAK-STAT/IFN-I axis central to SAMHD1 haploinsufficiency, but provides no mechanistic insight into cGAS-STING, NLRP3, VDAC1, or SAMHD1-specific pathways.
DOI: 10.1111/exd.70295

Coexisting ADAR and TSHB Mutations in an Infant With Retinal Detachment and Transient Cardiomyopathy. (from Neonatology/Pediatric Genetics)
Draidi Tamer; Khalil Mohammad; Kabaha Abed; Zuriqi Rafat; Masu'd Mohammad — 2026
Score: 4/10 | Pathways: AGS-spectrum, cGAS-STING, clinical-phenotype

This case documents ADAR-related AGS6, a type I interferonopathy sharing the AGS-spectrum with SAMHD1-related disease, but involves a different gene (ADAR), a distinct molecular mechanism (RNA editing failure rather than dNTPase/cGAS-STING), and the clinical novelty is the co-occurring TSHB mutation; the connection to SAMHD1 haploinsufficiency pathways is only via the broad interferonopathy/AGS diagnostic category.
DOI: 10.1155/crie/5534847

NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration (from Rheumatology/Orthopedics)
Peng Wan; Yimin Zheng — Frontiers in Immunology 2026
Score: 4/10 | Pathways: NLRP3, VDAC1, POLG-mtDNA, urate-NLRP3, other

This OA review touches on NF-κB as a hub integrating mitochondrial dysfunction-associated DNA sensing (obliquely referencing cGAS-STING/NLRP3 pathways) and DAMP-driven innate immune circuits that overlap mechanistically with the SAMHD1 interferonopathy framework, but remains disease-context-specific to cartilage degeneration with no direct relevance to SAMHD1, type I interferon, ISG15-mitophagy, or the family phenotype cluster.
DOI: 10.3389/fimmu.2026.1842443

Identification and diagnostic potential of pyroptosis-related genes in endometriosis: A novel bioinformatics analysis and validation. (from Gynecology/reproductive medicine)
Wang Li; Teng Piaopiao; Chen Jiawen; Ding Caiyun; Luo Xianchen — 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype, other

This paper investigates pyroptosis-related genes in endometriosis with some NLRP3/inflammasome relevance and touches on a gynecologic inflammatory condition, but the identified gene signatures (KIF13B, BAG6, MYO5A, HEATR2) have no direct connection to SAMHD1 pathways, cGAS-STING, or the core interferon-mitochondrial mechanism, making this only tangentially relevant via the shared pyroptosis/inflammasome biology and the family's endometrial carcinoma phenotype.
DOI: 10.1371/journal.pone.0350751

A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses. (from veterinary virology / antiviral therapeutics)
Yin Hongyan; Zhao Zhenchao; Wang Haiwei; Li Xin — 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, other

While the paper involves cGAS-DNA phase separation and innate immune signaling (cGAS-STING pathway) relevant to the disease mechanism, the context is entirely viral (SVV 3C protease in porcine systems) and addresses antiviral peptide inhibition rather than constitutive interferonopathy or SAMHD1-related pathology, making the connection tangential at best.
DOI: 10.1371/journal.ppat.1014291

Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System. (from Exercise physiology / sports medicine / neuroscience)
Zhu Xinyi; Shi Lei; Dong Yahong; Sun Yingjie; Jin Qiguan — 2026
Score: 3/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, other

This review covers mitochondrial quality control (biogenesis via PGC-1α/AMPK/SIRT1, mitophagy via PINK1/Parkin/mTOR, dynamics via Drp1) which are downstream components of the RED and PURPLE streams, but the paper is entirely focused on exercise as an intervention for brain aging with no connection to SAMHD1, interferonopathy, cGAS-STING, NLRP3, or the specific pathological context of this family.
DOI: 10.3390/biology15110854

The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System. (from Oncology/Cancer Biology)
Ghosh-Mitra Arpita; Patel Mansi; Das Samarjit — 2026
Score: 3/10 | Pathways: VDAC1, POLG-mtDNA, mTOR-lysosomal, other

This review covers EV-miRNA reprogramming of mitochondrial dynamics, fission/fusion, and intrinsic apoptosis in tumorigenesis, touching peripherally on mitochondrial dysfunction and immune regulation relevant to the disease mechanism, but does not address SAMHD1, cGAS-STING, NLRP3, ISG15, interferonopathy, or any direct pathway component with meaningful specificity.
DOI: 10.3390/ijms27115112

Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics. (from hepatology-nephrology-cardiology (fibrosis))
Feng Yourong; Zhang Xudong; Wang Xin Joy; Chen Chen — 2026
Score: 3/10 | Pathways: IRF7-metabolic, mTOR-lysosomal, other

This review covers metabolic reprogramming in fibrosis (Warburg effect, glycolysis, lipid metabolism) with some overlap in downstream metabolic consequences of mitochondrial dysfunction and NF-kB/inflammatory signaling, but does not address cGAS-STING, NLRP3, SAMHD1, interferonopathy, or the core pathways driving the A565T syndrome, making the connection tangential.
DOI: 10.1186/s43556-026-00490-9

Clonal lineage tracing of innate immune cells in human cancer. (from Oncology/Tumor Immunology)
Vincent Liu; Katalin D. Sandor; Patrick K. Yan; Zhuang Miao; Yajie Yin — Cancer cell 2026
Score: 3/10 | Pathways: POLG-mtDNA, other

While this paper uses somatic mtDNA mutations as lineage tracing barcodes to study innate immune clonal dynamics in the tumor microenvironment, its use of mtDNA is purely as a neutral genetic marker rather than addressing any mechanistic pathway relevant to SAMHD1 haploinsufficiency, cGAS-STING, NLRP3, or mitochondrial dysfunction in the disease context.
DOI: 10.1016/j.ccell.2026.05.006

Effect of nanobody-STING agonists on the tumor microenvironment and adoptive cell therapy for solid tumors. (from Oncology/Immunotherapy)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Journal of Clinical Oncology 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other

This paper involves STING pathway activation but purely in the context of tumor immunotherapy (adoptive cell therapy for solid tumors), with no mechanistic connection to SAMHD1 haploinsufficiency, interferonopathy, mitochondrial dysfunction, or the family phenotype constellation; the STING agonism here is an oncologic tool rather than an exploration of pathological constitutive cGAS-STING activation.
DOI: 10.1200/jco.2026.44.16_suppl.e14601

Abstract LB415: Nanobody:STING agonists reprogram the tumor microenvironment and improve adoptive cell therapy for solid tumors (from Oncology/Immuno-oncology)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Cancer Research 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other

While this paper involves STING pathway activation, it focuses on a nanobody-based tumor immunotherapy platform for solid tumors rather than any aspect of SAMHD1 haploinsufficiency, interferonopathy, or the downstream mitochondrial/inflammasome mechanisms relevant to the disease profile; STING is used here as a pharmacological target to enhance adoptive cell therapy, not in the context of constitutive cGAS-STING activation from mtDNA escape or SAMHD1 dysfunction.
DOI: 10.1158/1538-7445.am2026-lb415

Pathway Coverage This Week

other: 36 papers
cGAS-STING: 30 papers
NLRP3: 23 papers
POLG-mtDNA: 23 papers
VDAC1: 20 papers
treatment-target: 16 papers
ISG15-mitophagy: 15 papers
ME-CFS: 12 papers
JAK-STAT: 7 papers
clinical-phenotype: 6 papers
mTOR-lysosomal: 6 papers
dNTPase: 5 papers
AGS-spectrum: 4 papers
IRF7-metabolic: 3 papers
pregnancy-fetal: 1 papers
urate-NLRP3: 1 papers