Skip to content

nucleotide-rewiring

SAMHD1 Research Digest — 2026-09-09

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 13 papers evaluated | 1 high-relevance (≥7) | 6 medium (5–6) | 6 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Metabolic regulation of mitochondrial DNA (mtDNA) homeostasis. (from mitochondrial biology/metabolism)
Medeiros Tania Catarina; Calabrese Gaetano — Biochimica et biophysica acta. Molecular cell research 2026
Score: 7/10 | Pathways: POLG-mtDNA, mito-dNTP-transport, nucleotide-rewiring, dNTPase

This review directly addresses mitochondrial nucleotide pool regulation and POLG-driven mtDNA replication/quality control, mechanistically central to the PURPLE/GOLD streams of dGTP-driven mitochondrial dysfunction in SAMHD1 haploinsufficiency.
DOI: 10.1016/j.bbamcr.2026.120220

🟡 Medium Relevance (Score 5–6)

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

The Oxidative–Mitochondrial–Inflammatory Axis in Retinitis Pigmentosa: Extracellular mtDNA as Biomarker and Therapeutic Read-Out (from Ophthalmology (retinitis pigmentosa))
— Antioxidants 2026
Score: 6/10** | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target

This review details mtDNA release-driven cGAS-STING/TLR9/NLRP3 neuroinflammation via oxidative-mitochondrial dysfunction, directly paralleling the BLUE/PURPLE loops in SAMHD1 pathology though in a distinct retinal degeneration context.
DOI: 10.3390/antiox15091110

Understanding Dysfunctional Autophagy and Mitophagy in Inflammatory Cardiovascular Disease. (from Cardiology)
Michael E. Kaiser; Toni-ann Lewis; M. Malekan; Manish A. Parikh; Gioia Turitto — Cardiology in review 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, ISG15-mitophagy, clinical-phenotype

Details mitophagy/autophagy failure, mtDNA/DAMP release, and NLRP3-driven pyroptosis in cardiovascular inflammation, directly paralleling the mitochondrial-NLRP3-IL-1β mechanistic axis relevant to the SAMHD1 interferon-mitochondrial syndrome's cardiac phenotype risk.
DOI: 10.1097/crd.0000000000001302

Organelle-orchestrated cGAS-STING signaling and its role in neurodegeneration. (from Neurodegeneration/organelle biology)
Jin-Yue Liu; Sheng-ye Liu; Li-Xian Ran; Wenhao Qiao; Fan Zhang — Pharmacological research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

This review details organelle regulation of cGAS-STING (mitochondria, ER, MAMs, Golgi, lysosomes) and its role in chronic neuroinflammation, directly relevant to the BLUE loop mechanism (VDAC1/mtDNA/cGAS/STING/IFN-I) underlying the SAMHD1 A565T interferonopathy and its neurologic/AuDHD phenotypes, though it does not address SAMHD1 or NLRP3/NF-kB crosstalk directly.
DOI: 10.1016/j.phrs.2026.108216

Peroxiredoxin 6 limits mitochondrial peroxidation to prevent mitochondrial ER contact site assembly and inflammatory signalling following adaptive stress (from muscle physiology/redox biology)
PengLin Li; Yating Zheng; Jiwang Tang; Qin Xia; José C Casas-Martinez — bioRxiv 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial lipid peroxidation driving mtDNA release via MERCS/calcium dysregulation and innate immune activation, mechanistically paralleling the VDAC1-mtDNA-cGAS/NLRP3 axis central to SAMHD1 haploinsufficiency pathology even though SAMHD1 itself is not studied.
DOI: 10.64898/2026.07.24.740509

p300 Degradation by the p53-SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity. (from virology/molecular oncology (p53-SIAH1-p300 axis in antiviral immunity))
Yu Huidi; Zhan Zhihao; Pan Xiaoxiang; Zhang Xinyue; Liu Penggang — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Identifies p300-mediated TBK1 acetylation as a brake on IRF3-driven type I IFN production, directly relevant to the BLUE cGAS-STING-IRF3-IFN loop and NF-kB/IKK crosstalk central to the SAMHD1 interferonopathy model, though not SAMHD1-specific.
DOI: 10.1002/advs.76101

Next-Generation Genome Editing: Overcoming CRISPR-Cas9 Limitations with Prime Editing and PASTE Technology (from gene therapy/genome engineering)
Vikash Kumar; Aman Kumar; Balak Das Kurmi — Current Pharmacogenomics and Personalized Medicine 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing and PASTE technology relevant as a future correction strategy for a heterozygous missense variant like SAMHD1 A565T, but does not address SAMHD1 or its mechanisms directly.
DOI: 10.2174/0118756921492763260804044215

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Cell-Free Mitochondrial DNA as a Damage-Associated Molecular Pattern and Candidate Biomarker in Sickle Cell Disease Vaso-Occlusive Crisis: A Scoping Review (from Hematology (sickle cell disease))
Amoako Jerriod Paul Amoako; Owusu-Andoh Alexis; PSVV Charan; Atta-Poku Doris Ewu — 2026
Score: 4/10 | Pathways: cGAS-STING, VDAC1, clinical-phenotype

This scoping review discusses cf-mtDNA as a DAMP activating cGAS-STING-TBK1 in sickle cell vaso-occlusive crisis, mechanistically parallel to the BLUE loop but in a distinct disease with no SAMHD1 connection.
DOI: 10.21203/rs.3.rs-10864540/v1

ZBP1-mediated sensing of genomic stress in cancer therapy (from Oncology/cell death biology)
Xiao Zhong; Siddharth Balachandran; Ting Zhang — Ferroptosis and Oxidative Stress 2026
Score: 3/10 | Pathways: other

ZBP1/necroptosis/RIPK3 cancer-therapy pathway is a distinct innate nucleic-acid sensing axis with only tangential overlap (Z-RNA/R-loop stress) to SAMHD1's cGAS-STING/NLRP3/mitochondrial mechanisms, and no direct SAMHD1 or family-phenotype connection.
DOI: 10.70401/fos.2026.0035

Somatic Genome Editing in Cardiovascular Disease: Platforms, Targets, and Translational Progress (from cardiology/gene therapy)
Khawli George; Gorini Francesca; Palazzo Mariangela; Daher Jalil; Borghini Andre — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general review of somatic genome-editing platforms for cardiovascular disease (liver PCSK9/ANGPTL3/TTR, myocardial MYH7/MYBPC3) with no connection to SAMHD1, interferon/inflammasome pathways, or myeloid/immune cell correction strategies relevant to A565T.
DOI: 10.20944/preprints202609.0314.v1

Cascade-catalytic microneedles convert the tumor cholesterol shield into an oxidative spear for self-amplifying ferroptosis-driven cancer immunotherapy. (from Oncology/nanomedicine biomaterials engineering)
Rongjie Yang; Yu Zhang; Yushu Dong; Shuiling Chen; Ming Li — Biomaterials 2026
Score: 3/10 | Pathways: cGAS-STING

This paper uses cGAS-STING activation as a downstream immunotherapy mechanism in cancer nanomedicine, but is unrelated to SAMHD1 biology, dNTP metabolism, or the interferon-mitochondrial syndrome described in the disease profile.
DOI: 10.1016/j.biomaterials.2026.124474

From immune dysregulation to renal injury: mechanistic insights and translational opportunities in immune-mediated nephropathies. (from Nephrology)
Xiaoming Wang — Frontiers in cell and developmental biology 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, NF-kB-IKK, other

This nephrology review discusses cGAS-STING, NLRP3, NF-κB, and JAK-STAT pathways generically in immune-mediated kidney disease but has no direct connection to SAMHD1, its variants, or the documented family phenotypes.
DOI: 10.3389/fcell.2026.1878787

Single-Cell and Spatial Transcriptomics Define Eosinophil Heterogeneity during Influenza A Virus-induced Exacerbation of Fungal Allergic Asthma in C57BL/6 mice. (from pulmonology/immunology (allergic asthma and influenza))
Veltri Anthony J; Wells Anthony J; Baus Magdaline; Mathur Sameer K; Samarasinghe — Journal of leukocyte biology 2026
Score: 3/10 | Pathways: JAK-STAT, other

Samhd1 appears only as one of many interferon-stimulated genes noted in a mouse eosinophil single-cell transcriptomics study of flu/asthma, with no mechanistic or clinical link to SAMHD1 haploinsufficiency or the syndrome described.
DOI: 10.1093/jleuko/qiag120

Pathway Coverage This Week

  • cGAS-STING: 6 papers
  • NLRP3: 4 papers
  • treatment-target: 4 papers
  • other: 3 papers
  • POLG-mtDNA: 2 papers
  • mito-ROS-NF-kB: 2 papers
  • clinical-phenotype: 2 papers
  • VDAC1: 2 papers
  • NF-kB-IKK: 2 papers
  • prime-editing: 2 papers
  • gene-therapy-delivery: 2 papers
  • JAK-STAT: 2 papers
  • mito-dNTP-transport: 1 papers
  • nucleotide-rewiring: 1 papers
  • dNTPase: 1 papers
  • ISG15-mitophagy: 1 papers

Structural and single-molecule insights into the core human mitochondrial DNA replisome

The finding

This review integrates recent cryo-EM and single-molecule studies to build a quantitative mechanistic framework for how the core human mitochondrial replisome—POLG, Twinkle, and mtSSB—coordinates replication of the light and heavy strands of mtDNA. The authors synthesize structural data on replisome architecture with dynamic measurements of fork progression, describing how initiation, elongation, and regulation are achieved at the mitochondrial replication fork, and identify remaining gaps toward a complete mechanistic model.

Where it fits

This paper speaks directly to Loop B (Mitochondrial/NLRP3) in the SAMHD1 A565T model—specifically, the proposed mechanism by which dNTP pool expansion causes POLG replisome stress. The model posits that excess cytosolic dNTPs flood mitochondrial carriers, perturb the matrix pool, and stall POLG, leading to oxidized mtDNA (8-OHdG) and VDAC1 destabilization, which licenses the NLRP3 inflammasome. This review provides the structural and kinetic context for why POLG is vulnerable to nucleotide imbalances: the replisome must coordinate leading- and lagging-strand synthesis with a tightly regulated dNTP supply, and asymmetric pools—exactly what a partial loss-of-function SAMHD1 variant would produce—could plausibly stall the polymerase and generate the replication stress that feeds the downstream inflammatory cascade. The single-molecule approaches highlighted here are particularly relevant, as they can directly probe how POLG kinetics respond to altered dNTP concentrations and ratios.

Caveats

  • This is a review, not a primary study; the mechanistic claims are synthesized from other groups' work, not newly demonstrated here.
  • The paper does not address SAMHD1 or any disease variant—it describes the wild-type replisome under normal conditions, not the perturbed state induced by dNTP pool expansion.
  • Structural and single-molecule data come from reconstituted in vitro systems, which may not fully capture the mitochondrial environment (e.g., membrane tethering, local nucleotide compartmentalization) relevant to the A565T pathology.

What to watch

The next key question is whether single-molecule POLG assays can be run under asymmetric dNTP pools mimicking the SAMHD1 A565T state—if POLG stalling is directly observable under those conditions, it would provide a mechanistic bridge from the enzyme defect to the oxidized mtDNA that primes NLRP3.

Source: Structural and single-molecule insights into the core human mitochondrial DNA replisome — 2026.

SAMHD1 Research Digest — 2026-08-16

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 29 papers evaluated | 2 high-relevance (≥7) | 14 medium (5–6) | 13 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis. (from Aerospace/regenerative medicine (stem cell biology under microgravity))
Huang Lei; Huang Rui; Lv Wenjun; Li Zimeng; Tu Yun — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target

This paper directly demonstrates the BAK/BAX-VDAC-mediated mtDNA leakage → cGAS-STING activation axis (BLUE stream) driving cellular senescence, mechanistically paralleling the core interferon-mitochondrial pathway implicated in the SAMHD1 A565T syndrome, with STING inhibition (C176) shown as a viable therapeutic strategy.
DOI: 10.1002/jcp.70220

Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models (from Neurology/Neurodegeneration (Alzheimer's disease))
Tian Mao; Zhu Xiuping; Lei Zhifeng; Lu Yongheng; Mo Lin — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA leakage-driven cGAS-STING-TBK1-IRF3-NFκB neuroinflammation as an upstream pathogenic mechanism directly analogous to the BLUE/RED loops in the SAMHD1 interferon-mitochondrial syndrome, with a novel therapeutic (Taulipro) targeting the mtDNA leakage step relevant to future treatment strategies.
DOI: 10.21203/rs.3.rs-10416296/v1

🟡 Medium Relevance (Score 5–6)

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

Honokiol targets cyclophilin D and blocks mitochondrial DNA release to inhibit microglial NLRP3 inflammasome activation and alleviate neurodegeneration in Parkinson's disease models. (from Neurology/neurodegeneration (Parkinson's disease) and natural product pharmacology)
Gan Qinglin; Xian Yingtong; Zhou Ting; Fu Xiaolong; Gou Shiyi — Chemico-biological interactions 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

This paper demonstrates mtDNA release triggering NLRP3 inflammasome activation via mitochondrial permeability transition (CypD), mechanistically parallel to the VDAC1/mtDNA-NLRP3 axis central to the SAMHD1 syndrome, and offers a small-molecule therapeutic (honokiol) strategy relevant to inflammasome modulation.
DOI: 10.1016/j.cbi.2026.112305

Hepatocyte hnRNPK preserves mitochondrial integrity to restrain liver injury and fibrosis. (from Hepatology)
Peng Qian; Wang Sujuan; Zhang Yufeng; Luo Yangjun; Lan Beiwu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This paper demonstrates mitochondrial fragmentation (via OPA1 splicing dysregulation) leading to cytosolic mtDNA release and cGAS-STING activation driving fibrotic inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA-cGAS-STING) in the SAMHD1 profile despite a different upstream trigger and hepatic rather than systemic context.
DOI: 10.1097/hep.0000000000001836

TANK-binding kinase 1 (TBK1): unexpected cell type-specific immune regulation beyond antiviral type I interferon signaling. (from virology/vaccinology)
Almeida Mariana S; Bezbradica Jelena S; Coban Cevayir — Current opinion in virology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

TBK1 is the key non-canonical IKK kinase (IKKe/TBK1 partner) linking cGAS-STING/IRF3 to both IFN-I and NF-kB signaling, and this review's discussion of cell-type-specific TBK1 functions and pharmacological inhibition is directly relevant to the STING-IRF3-NFkB crosstalk axis and potential therapeutic targeting in the interferonopathy mechanism.
DOI: 10.1016/j.coviro.2026.101545

Structural and single-molecule insights into the core human mitochondrial DNA replisome. (from structural biology/biochemistry)
Plaza-G A Ismael; Miguez-Amil Samuel; Hayes Allison M; Ciesielski Grzegorz L; Fe — The Biochemical journal 2026
Score: 6/10 | Pathways: POLG-mtDNA, mito-dNTP-transport

Detailed structural insight into the Polγ/Twinkle/mtSSB replisome is directly relevant to the POLG-stalling and mtDNA replication stress steps implicated in the PURPLE pathway of this syndrome's mechanism.
DOI: 10.1042/BCJ20260373

Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation (from Microbiology/gastroenterology (gut microbiome-mitochondria crosstalk))
Xinxing Lu; Wenbin Sun; Daowei Zhang; Bin Hou; Huiyu Tai — Frontiers in Cellular and Infection Microbiology 2026
Score: 6/10 | Pathways: NLRP3, cGAS-STING, ISG15-mitophagy, mito-ROS-NF-kB, other

Reviews mtDNA-driven cGAS-STING/NLRP3 activation and PINK1/Parkin mitophagy as general mechanisms overlapping core disease pathways, though framed via gut microbiome rather than SAMHD1-specific dysregulation.
DOI: 10.3389/fcimb.2026.1866924

cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders. (from Neurology/Neuroimmunology)
Rahim Abdul; Zubair Shaik Mahammad; Ahamed Mustak; Das Soumi; Patel Royal — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This review details cGAS-STING/mtDNA-driven neuroinflammation (Loop A) and its therapeutic targeting, relevant to the AuDHD/neurological phenotype in the SAMHD1 family though not SAMHD1-specific.
DOI: 10.1007/s11481-026-10307-9

Subacute ruminal acidosis induces colonic inflammation and barrier damage via cGAS-STING pathway in Hu sheep fed a high-grain diet. (from Veterinary gastroenterology/animal science)
Meng Meijuan; Shi Xiaoli; Tu Yuanlu; Bai Yunfeng; Chang Guangjun — 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA release triggering cGAS-STING/NF-κB pathway activation and downstream inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA/cGAS-STING) in the SAMHD1 syndrome model despite being an unrelated ruminant/agricultural species and disease context.
DOI: 10.1016/j.jnutbio.2026.110483

Vilazodone inhibits NLRP3 inflammasome assembly by targeting the NACHT domain and alleviates inflammatory disease. (from psychiatry/pharmacology (antidepressant drug repurposing))
Yang Xiangyu; Xiong Guifang; Yang Jie; Ma Xinyi; Qie Yuanzheng — International immunopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Vilazodone directly inhibits NLRP3 inflammasome assembly (NACHT domain) and reduces MSU-induced inflammation, offering a potential repurposed therapeutic candidate relevant to the GOLD (uric acid/MSU-NLRP3) and general NLRP3 hyperactivation streams in this interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.117279

Novel natural inhibitor Rubimaillin targets NLRP3 R167/Y381 to ameliorate inflammatory and neurodegenerative diseases. (from Ethnopharmacology/natural product drug discovery)
Xiao Jing; Lan Zhen; Zhang Ran; Zhang Jie; Hu Zuobin — Journal of ethnopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Identifies a natural NLRP3 inhibitor effective in gouty arthritis (MSU-induced, matching the GOLD pathway) and neurodegenerative models, offering a potential therapeutic candidate relevant to the NLRP3 hyperactivation axis in this syndrome.
DOI: 10.1016/j.jep.2026.122293

Lactate-Induced K370 Lactylation of STING Inhibits STING-TBK1 Signaling and Dampens Anti-Tumor Immunity. (from oncology/tumor immunometabolism)
Wu Yueyao; Wang Jingzhe; Chen Xu; Yang Yuntong; Wei Ping — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Reveals a novel post-translational (lactylation) regulatory checkpoint on STING-TBK1 signaling relevant to the BLUE loop's IFN-I output, though in an oncology/tumor immunity context rather than SAMHD1 interferonopathy.
DOI: 10.1002/advs.77209

Mechanistic machine learning for prediction of prime editing outcomes. (from computational genome editing / bioengineering)
Hsu Alvin; Chen Peter J; Li Angus H; Hemez Colin F; Gao Xin D — Nature biotechnology 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents a machine learning tool (OptiPrime) for optimizing prime editing efficiency, directly relevant to future gene correction strategies for missense mutations like SAMHD1 p.A565T, though it does not address SAMHD1 or the interferon-mitochondrial mechanism itself.
DOI: 10.1038/s41587-026-03261-7

Advances in paclitaxel-mediated remodeling of the gastric cancer immune microenvironment and sensitization to immune checkpoint inhibitors via cGAS-STING pathway activation triggered by mtDNA release: challenges and translational perspectives. (from Oncology (gastric cancer chemo-immunotherapy))
Wu Chu-Ying; Sun Zun-Long; Ye Kai — 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target, other

Describes mtDNA release activating cGAS-STING/type I interferon signaling, mechanistically overlapping with the BLUE loop, but in an oncology chemotherapy context unrelated to SAMHD1 or the family phenotype.
DOI: 10.1007/s11033-026-12570-8

Mitochondrial Dysfunction as a Driver of Meta-Inflammation in Aging: The Emerging Role of PDK4 in Bioenergetic Reprogramming and Inflammatory Amplification. (from metabolic/aging biology and endocrinology)
Chowdhury Md Riad; Jeong Gui-Hwa; Lee In-Kyu — 2026
Score: 5/10 | Pathways: NLRP3, cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, other

Reviews mitochondrial dysfunction driving NF-κB/NLRP3/cGAS-STING-mediated meta-inflammation via PDK4/pyruvate metabolism, an adjacent metabolic-inflammatory mechanism relevant to the family's mitochondrial-interferon axis but not SAMHD1-specific.
DOI: 10.3390/cells15151404

eVLP compound delivery breaks the prime editing efficiency ceiling. (from gene therapy/genome editing engineering)
Wang Margaret R; Sánchez-Rivera Francisco J — Cell genomics 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Describes an engineered virus-like particle (eVLP) repeated-dosing strategy (PRIME-VLP) that improves prime editing efficiency, relevant as a potential future delivery platform for correcting SAMHD1 point mutations but not disease-mechanism specific.
DOI: 10.1016/j.xgen.2026.101333

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Non-Invasive Scalp Tape-Strip RNA Sequencing Captures Disease Activity and Treatment-Response Signatures in Alopecia Areata. (from Dermatology)
Mochón-Jiménez Carmen; Gay-Mimbrera Jesús; Dávila-Flores Viviana; He Helen; Zhou — Allergy 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Alopecia areata tape-strip transcriptomics highlights IFN/JAK-STAT and baricitinib response signatures, mechanistically adjacent to the interferonopathy axis but not connected to SAMHD1 or the family's core mitochondrial-inflammasome pathways.
DOI: 10.1111/all.70293

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2 (from genomics/bioinformatics methodology)
Tingting Cong; Runda Xu; Xuancheng Chen; Junsong Yuan; Zuomiao Lin — Nature Communications 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents an off-target detection method for CRISPR editors relevant to future gene correction of SAMHD1 variants but has no direct disease mechanism or immune pathway content.
DOI: 10.1038/s41467-026-76778-9

Inflammatory kinase TBK1 suppresses homologous recombination DNA repair to sensitize tumors to chemotherapy. (from Oncology/DNA damage response)
Zhou Wei; Wang Xiangyu; Steigleder Susanne S; Xing Aowei; Yang Dan — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 4/10 | Pathways: NF-kB-IKK, other

TBK1 (IKKε/TBK1 axis) is a named kinase in the interferonopathy mechanism, but this paper focuses on its DNA-repair/chemotherapy role independent of cytokine or STING/IRF3 signaling, making it only tangentially relevant.
DOI: 10.1073/pnas.2533402123

Prime Editing Mediated Generation and Correction of the mdx5cv Mutation Restores Dystrophin Expression in Myoblasts (from Neuromuscular genetics / gene therapy)
A. Siddika; F. Husseiny; J. Rousseau; J. Tremblay — International Journal of Molecular Sciences 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

Demonstrates a generalizable prime editing correction workflow for a pathogenic point mutation restoring protein expression, methodologically relevant to future SAMHD1 A565T correction but unrelated disease (DMD) and non-immune cell type.
DOI: 10.3390/ijms27156927

In Vivo Base Editing for Neonatal Inborn Errors of Metabolism: Clinical Progress, N-of-1 Therapy, and the Ethics of Bespoke Genetic Medicine. (from Neonatology/Genetic Medicine Ethics)
Li Oscar Mingtian; Li Yijiang; Li Summer Xia Tian — Cureus 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

This paper reviews in vivo base editing for neonatal metabolic disorders using LNP delivery, relevant as a generalizable precedent for correcting a heterozygous missense variant like SAMHD1 A565T but not targeting immune/myeloid cells or the interferon-mitochondrial mechanism directly.
DOI: 10.7759/cureus.114354

From mechanical adaptation to innate immune reprogramming in osteoarthritis: a load-immunity framework (from Orthopedics/Rheumatology (mechanobiology of joint disease))
Shiguo Zuo; Lijun He; Z. Hou; Quanliang Tian; Yilong Yang — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, other

This osteoarthritis review discusses cGAS-STING and NLRP3 signaling in mechanotransduction and mitochondrial danger signal propagation, mechanistically adjacent but not directly tied to SAMHD1 biology or the interferon-mitochondrial syndrome described.
DOI: 10.3389/fimmu.2026.1931112

Liver Organoids: From Disease Modelling to Regenerative Medicine. (from Hepatology/regenerative medicine)
Wang Tiepeng; Qu Xiaotian; Si Jinhong; Meng Junkang; Zhang Ting — Cell proliferation 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general liver organoid review with only a passing mention of prime editing correction in patient-derived organoids and no SAMHD1, interferon, NLRP3, or mitochondrial dNTP pathway content relevant to the family phenotype.
DOI: 10.1111/cpr.70268

Hierarchical Core-Shell Nanoplatform with Sequential Mn<sup>2+</sup>/Co<sup>2+</sup> Release Enables Dual-Track STING Amplification and Radiosensitization for Potent Radio-Metalloimmunotherapy. (from Oncology/nanomedicine radiotherapy)
Luo Baiyi; Xiang Qingming; Xie Yingling; Wang Shuo; Xu Yu — 2026
Score: 3/10 | Pathways: cGAS-STING

Paper uses cGAS-STING pathway activation as a cancer nanomedicine strategy via metal ion delivery, unrelated to SAMHD1 mechanism or mitochondrial dNTP dysregulation despite shared pathway terminology.
DOI: 10.1016/j.actbio.2026.08.012

Estrogen Withdrawal-Induced Cognitive Impairment in Menopausal Women: Mechanisms and Prospects for Integrated Interventions. (from Neurology/Endocrinology)
Qiu Tiantian; Zhang Junying; Zhao Jiayou — International journal of molecular sciences 2026
Score: 3/10 | Pathways: NLRP3, mito-ROS-NF-kB

Discusses NLRP3 inflammasome and mitochondrial dysfunction in menopausal cognitive decline, sharing mechanistic overlap with the interferon-mitochondrial syndrome but unrelated to SAMHD1 or its specific pathways.
DOI: 10.3390/ijms27157003

The APC/C subunit APC7 exerts antiviral effects by targeting the adaptor protein MAVS (from Virology/cell biology (RIG-I-MAVS antiviral signaling))
Rui Su; Aiping Sun; Yifan Niu; Tiesuo Zhao; Hui Wang — Frontiers in Immunology 2026
Score: 3/10 | Pathways: other

This paper concerns RIG-I/MAVS antiviral signaling and IFN-I induction via a distinct APC7-MAVS ubiquitination mechanism, not overlapping with SAMHD1/cGAS-STING/NLRP3/NF-kB pathways central to the disease profile.
DOI: 10.3389/fimmu.2026.1912055

Extracellular vesicle-mediated immune crosstalk in rheumatoid arthritis synovium: mechanistic insights and translational challenges (from Rheumatology)
Feng Luo; Xuemei Yuan; Heng Zhou; Qiuyi Wang; Changming Chen — Frontiers in Immunology 2026
Score: 3/10 | Pathways: cGAS-STING, JAK-STAT, NF-kB-IKK, clinical-phenotype

This RA-focused review touches on cGAS-STING, NF-κB, and JAK-STAT signaling and mentions RA (a tracked family phenotype), but it centers on extracellular vesicle biology in synovium without any connection to SAMHD1, dNTP metabolism, or the core mitochondrial-interferon mechanism.
DOI: 10.3389/fimmu.2026.1891984

Targeting the hallmarks of ageing: Pharmacological challenges and breakthroughs in CRISPR delivery systems and future prospects. (from Gerontology/pharmacology (CRISPR delivery technology))
Rathore Sakshi; Gupta Akash; Shah Kamal; Chauhan Nagendra Singh; Gupta Sanjay Ku — Ageing research reviews 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR delivery/ageing review with only generic mention of prime/base editing and mitochondrial dysfunction, lacking any SAMHD1, immune, or myeloid-specific delivery focus relevant to this disease.
DOI: 10.1016/j.arr.2026.103301

Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases. (from Pediatric Rheumatology/Nephrology)
Kousa Alyamama; Alhamwi Ahmad; Alsayed Mohammad Khaled; Jabaly Sara; Khalil Bash — Medicine 2026
Score: 3/10 | Pathways: AGS-spectrum, clinical-phenotype, treatment-target

DNASE1L3 monogenic lupus is a distinct autosomal-recessive nucleic acid clearance disorder in the broader interferonopathy/autoimmune spectrum, but does not involve SAMHD1, dNTPase, cGAS-STING, or the mitochondrial-NLRP3 axis central to this profile, though baricitinib use is a tangential JAK-inhibitor overlap.
DOI: 10.1097/MD.0000000000050283

Pathway Coverage This Week

  • cGAS-STING: 13 papers
  • treatment-target: 13 papers
  • NLRP3: 7 papers
  • prime-editing: 7 papers
  • gene-therapy-delivery: 7 papers
  • NF-kB-IKK: 6 papers
  • other: 6 papers
  • mito-ROS-NF-kB: 4 papers
  • clinical-phenotype: 4 papers
  • POLG-mtDNA: 2 papers
  • urate-NLRP3: 2 papers
  • JAK-STAT: 2 papers
  • VDAC1: 1 papers
  • mito-dNTP-transport: 1 papers
  • ISG15-mitophagy: 1 papers
  • AGS-spectrum: 1 papers

SAMHD1 Research Digest — 2026-07-29

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 12 papers evaluated | 3 high-relevance (≥7) | 8 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Mitophagy mitigates mitochondrial DNA-induced activation of cGAS-STING in autoimmune thyroiditis (from Endocrinology/Rheumatology—autoimmune thyroiditis model provides orthogonal evidence for cGAS-STING-driven tissue-specific autoimmunity that bridges to systemic interferonopathy phenotype in multi-system SAMHD1 families.)
Xiao-Chen Xie; Yang Guo; Ran Guo; Yong-Ze Li; Shan-Shan Wang — Nature Communications 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, POLG-mtDNA, mito-ROS-NF-kB, treatment-target, clinical-phenotype

Directly demonstrates mtDNA-cGAS-STING axis driving autoimmune disease via impaired mitophagy (PINK1/Parkin/TAX1BP1), mechanistically overlapping with the RED and BLUE loops in SAMHD1 A565T haploinsufficiency; identifies STING inhibition as therapeutic target applicable to convergent interferonopathy.
DOI: 10.1038/s41467-026-76047-9

NLRP3 Inhibitor KBD3536 Attenuates Acute Inflammation, Radiation-Induced Skin Injury, and Early Metabolic Dysfunction in Preclinical Models. (from Pharmacology/medicinal chemistry (NLRP3 inhibitor drug discovery and preclinical efficacy testing))
Qian Xinying; Ye Fei; Li Zhiyong; Chu Hongzhu; Xu Zeng — Pharmaceuticals (Basel, Switzerland) 2026
Score: 7/10 | Pathways: urate-NLRP3, NLRP3, NF-kB-IKK, treatment-target, clinical-phenotype

KBD3536 is a novel NLRP3 inhibitor with demonstrated efficacy in MSU-induced acute inflammation (gouty arthritis) and HFD-induced metabolic dysfunction—two pathologies directly implicated in the SAMHD1 A565T family phenotype (dGTP → purine catabolism → uric acid → MSU-NLRP3 axis; hepatic steatosis via IRF7-metabolic reprogramming); the paper provides preclinical validation of NLRP3 inhibition as a therapeutic strategy for this converged interferonopathy-metabolic syndrome.
DOI: 10.3390/ph19071083

CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence. (from Cell biology/gerontology—lysosomal biology and senescence mechanotransduction, not traditionally part of immunology or rheumatology training.)
Yin Jian; Gao Yizhou; Jing Yaobin; Jiang Xiaoyu; Wang Feibo — Protein & cell 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, mTOR-lysosomal, treatment-target

GNPTAB-STING noncanonical activation via direct protein-protein interaction (E1119 interface) provides a novel upstream STING priming mechanism independent of canonical cGAS-mtDNA sensing; this represents an alternative route to STING/TBK1/NF-κB axis hyperactivation relevant to the BLUE and NF-κB crosstalk loops in A565T interferonopathy, with actionable therapeutic potential (STING-GNPTAB interface antagonism) for suppressing senescence-associated STING amplification.
DOI: 10.1093/procel/pwag049

🟡 Medium Relevance (Score 5–6)

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

DNAJB12/14 redox switching directs chaperone- and Bax/Bak-dependent ER protein reflux. (from Cell biology / ER stress and proteostasis; redox biochemistry)
Abu Madegam Laila; Gavriel Noa; Adebisi Raifu Tolulope; Igbaria Aeid — Redox biology 2026
Score: 6/10 | Pathways: BIK-cancer, mTOR-lysosomal, NF-kB-IKK, apoptosis-autophagy switch

BIK-mediated BAX/BAK recruitment to ER during severe ER stress mechanistically overlaps with the apoptosis-autophagy switch dysregulated in SAMHD1 haploinsufficiency, where ISGylation of BH3-only proteins and mitochondrial damage drive cell death; redox-sensitive DNAJB chaperone control of proteostasis and ER-to-cytosol signaling may modulate the severity of interferonopathy-driven ER stress in this family.
DOI: 10.1016/j.redox.2026.104324

Pectolinarigenin Attenuates LPS-Induced Lung Inflammation and Injury with Reduced HDAC3/NF-κB/NLRP3 Signaling. (from Pulmonology/immunotoxicology; plant natural products pharmacology)
Kim Danbee; Lee Dong-Keon; Park Jeong-Ran — Antioxidants (Basel, Switzerland) 2026
Score: 6/10 | Pathways: NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, treatment-target

Pectolinarigenin directly modulates the HDAC3/NF-κB/NLRP3 axis in LPS-induced inflammation, addressing two key steps in the proband's pathophysiology: NF-κB transcriptional priming of NLRP3 (Signal 1) and NLRP3 inflammasome activation (Signal 2); HDAC3 inhibition is a mechanistically novel approach to breaking the NF-κB–NLRP3 feed-forward loop and reducing mitochondrial ROS-driven inflammation, though the study uses acute LPS challenge rather than the chronic mitochondrial dNTP–oxMtDNA–NLRP3 circuit specific to SAMHD1 haploinsufficiency.
DOI: 10.3390/antiox15070898

Evolutionary history and recombination in the mitochondrial carrier SLC25 superfamily analyzed by similarities in the exon and transmembrane α‐helix sequences (from Evolutionary biology / structural proteomics)
Magnus Monné; D. V. Miniero; R. Calvello; A. Cianciulli; Luigi Palmieri — Protein Science : A Publication of the Protein Society 2026
Score: 6/10 | Pathways: mito-dNTP-transport, nucleotide-rewiring, other

This evolutionary/structural analysis of SLC25 superfamily (including PNC1/PNC2 nucleotide carriers) provides mechanistic foundation for understanding how substrate-specific subfamilies arose, directly relevant to the PNC1/2-mediated mitochondrial dNTP import bypass that drives NLRP3 hyperactivation in SAMHD1 haploinsufficiency; exon recombination patterns could illuminate functional specialization of dNTP transporters.
DOI: 10.1002/pro.70727

Synthetic Toll-Like Receptors for Control of Innate Immunity With Far-Red Light. (from Synthetic optogenetics/photobiology—a tool discipline offering potential mechanistic insight and future targeting strategy for the NF-κB and interferon regulatory axis but without direct mitochondrial, dNTPase, or disease-specific validation.)
Leopold Anna V; Verkhusha Vladislav V — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: NF-kB-IKK, IRF7-metabolic, treatment-target

Synthetic TLR optogenetics with MyD88→NF-κB/IRF3/IRF7 axis reprogramming is mechanistically adjacent to the NF-κB priming of NLRP3 and the dual IKKε-driven NF-κB + IRF7 crosstalk that sustains the convergent interferon–mitochondrial syndrome in SAMHD1 p.A565T haploinsufficiency; optical dissection of TLR→MyD88→NF-κB/IRF signaling could reveal druggable nodes in the IKK-NEMO complex and IRF7-metabolic amplification loop.
DOI: 10.1002/advs.202520640

Targeting the NLRP3/Caspase-1 pyroptotic pathway exacerbates insulin resistance upon exposure to nanoplastics with different surface chemistries. (from Environmental toxicology and metabolic disease; bridges to rare disease through convergent NLRP3-inflammasome-insulin-resistance axis and mitochondrial dysfunction phenocopy of SAMHD1 haploinsufficiency.)
Yao Xinxin; Cao Yu; Lin Sue; Chen Shihua; Xie Feiqin — Journal of hazardous materials 2026
Score: 6/10 | Pathways: NLRP3, mitochondrial-ROS-NF-kB, oxidative-stress-mtDNA, metabolic-dysfunction-insulin-resistance, inflammasome-pyroptosis, other

Paper demonstrates NLRP3/caspase-1 pyroptotic activation downstream of nanoplastic-induced mitochondrial dysfunction and cytosolic mtDNA accumulation in metabolic stress (hyperglycemia/insulin resistance), directly modeling the PURPLE-loop mechanism (ox-mtDNA → NLRP3) and BLUE-loop (mtDNA escape → inflammasome) operative in SAMHD1 A565T haploinsufficiency; validates NLRP3 inhibition as partial rescue strategy for metabolic phenotypes, but lacks SAMHD1, dNTPase, or dNTP-mediated mechanism, and uses exogenous environmental trigger rather than genetic haploinsufficiency.
DOI: 10.1016/j.jhazmat.2026.143078

Astilbin Alleviates Gouty Arthritis via Regulating NLRP3 Inflammasome and NF-κB Signaling Pathway: A Comprehensive Study on In Vitro and In Vivo Experimental Models. (from Rheumatology/Pharmacology (natural product anti-inflammatory); mechanism-of-action study demonstrating dual NLRP3–NF-κB inhibition in gouty arthritis model, transferable to dNTP-driven NLRP3 hyperactivation in SAMHD1-deficient states.)
Zhang Xiaoxi; Fu Gaoyang; Zhao Xinyu; Huang Yan; Li Fenfen — Nutrients 2026
Score: 6/10 | Pathways: urate-NLRP3, NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, treatment-target

Astilbin suppresses MSU-crystal–induced NLRP3 inflammasome and NF-κB signaling (P-p65, P-IKKα, P-IκBα, cleaved-caspase-1), directly targeting the GOLD pathway (dGTP → uric acid → MSU → NLRP3) and the NF-κB priming axis that sustains IL-1β autocrine amplification in SAMHD1 haploinsufficiency; relevant as a potential adjunctive therapeutic for the inflammatory arm of convergent interferon–mitochondrial syndrome in this family.
DOI: 10.3390/nu18142360

Blood transcriptome bridges orthogonal immunotypes and gut microbiome enterotypes in humans. (from Microbiome/Metabolomics)
Affaticati Fabio; Ha My K; Gehrmann Thies; De Boeck Ilke; Kuznetsova Mariia — Cell reports 2026
Score: 6/10 | Pathways: NF-kB-IKK, JAK-STAT, NLRP3, clinical-phenotype

Blood transcriptome integration identifies two distinct inflammatory profiles—interferon-driven versus NF-κB/IL-6-driven—that directly map to the divergent activation streams (BLUE interferon loop vs. PURPLE/GOLD NLRP3 loops) in SAMHD1 A565T haploinsufficiency; gut microbiota-immune axis bridging is relevant to family's reported gastrointestinal heterogeneity and immunotype stratification in interferonopathy populations.
DOI: 10.1016/j.celrep.2026.117752

Evaluation of Zebularine as a Potential DNA Methyltransferase 1 Inhibitor Associated With SAMHD1 Expression in Cancer Cells (from Oncology)
Muhammad Zeeshan Ahmed; Mahnoor Fatima; Ayesha Shahbaz; Zeeshan Mutahir — ChemistrySelect 2026
Score: 5/10 | Pathways: BIK-cancer, SAMHD1, treatment-target

Zebularine modulates SAMHD1 expression in prostate cancer cells (relevant to BIK-prostate axis and SAMHD1 as tumor suppressor in family phenotype), but mechanistic connection is via DNMT1 epigenetic silencing rather than dNTPase activity, mitochondrial dysfunction, or interferonopathy pathways central to A565T haploinsufficiency.
DOI: 10.1002/slct.73893

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response. (from Virology/Oncology (KSHV tropism and persistent infection pathogenesis, not immunometabolic or rare disease))
Yu Caroline J; Damania Blossom — PLoS pathogens 2026
Score: 3/10 | Pathways: IRF3, cGAS-STING, JAK-STAT, other

VRK3 suppresses IRF3 and TBK1 activation in KSHV infection, which intersects the cGAS-STING→IRF3→IFN-I axis (BLUE Loop), but lacks SAMHD1 involvement, mitochondrial pathology, dNTP metabolism, NLRP3, or direct relevance to the A565T haploinsufficiency mechanism driving the convergent interferon–mitochondrial syndrome.
DOI: 10.1371/journal.ppat.1014400

Pathway Coverage This Week

  • treatment-target: 7 papers
  • NF-kB-IKK: 7 papers
  • NLRP3: 5 papers
  • cGAS-STING: 3 papers
  • clinical-phenotype: 3 papers
  • other: 3 papers
  • urate-NLRP3: 2 papers
  • mTOR-lysosomal: 2 papers
  • BIK-cancer: 2 papers
  • NF-kB-NLRP3-priming: 2 papers
  • JAK-STAT: 2 papers
  • VDAC1: 1 papers
  • ISG15-mitophagy: 1 papers
  • POLG-mtDNA: 1 papers
  • mito-ROS-NF-kB: 1 papers
  • apoptosis-autophagy switch: 1 papers
  • mito-dNTP-transport: 1 papers
  • nucleotide-rewiring: 1 papers
  • IRF7-metabolic: 1 papers
  • mitochondrial-ROS-NF-kB: 1 papers
  • oxidative-stress-mtDNA: 1 papers
  • metabolic-dysfunction-insulin-resistance: 1 papers
  • inflammasome-pyroptosis: 1 papers
  • SAMHD1: 1 papers
  • IRF3: 1 papers

↩ Re-run 08:33 UTC | Model: claude-sonnet-5

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

🟡 Medium Relevance

Multiple Roles of G3BP1 in Regulating STING-Dependent Interferon and Cytokine Induction by Cytosolic dsDNA and HSV-1 Infection. (from Virology/cell stress biology)
Trupti Devale; Praveen Manivannan; K. Malathi — Viruses 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Details G3BP1 as a regulator of cGAS-STING signaling (STING Golgi trafficking, IFN/cytokine output) directly relevant to the BLUE loop mechanism underlying the SAMHD1 interferonopathy, though it does not involve SAMHD1 itself.
DOI: 10.3390/v18070719

Mitochondrial dynamics and metabolic regulation in cellular inflammation: From mechanisms to precision therapeutics

The finding

This is a review article, not a primary research study — it doesn't report new experimental data. Its contribution is synthesis: it pulls together current literature on how mitochondrial fission/fusion balance (largely governed by Drp1-driven fission versus fusion machinery) acts as a "metabolic checkpoint" that licenses NLRP3 inflammasome activation, and it catalogs how oxidized/ribonucleotide-containing mtDNA released from fragmented mitochondria acts as a hyper-immunogenic ligand for cGAS-STING and other cytosolic sensors. It also surveys pharmacological strategies (Drp1 inhibitors, GLP-1 agonists, mitochondrial transplantation, etc.) aimed at this axis across diseases like sepsis, osteoarthritis, and cancer.

Where it fits

For the SAMHD1 A565T model, this review speaks most directly to Arm 2 (mitochondrial) and its intersection with Arm 3 (nucleotide/NLRP3). Two threads are especially relevant: (1) the idea that fragmented mitochondria release mtDNA that is only immunogenic when "fragile" or oxidized — a concept that dovetails with our hypothesis that SAMHD1 dysfunction leads to dNTP-pool imbalance, oxidized mtDNA, and NLRP3 activation; and (2) the general framework linking mitochondrial quality control (fission/fusion, mitophagy) to cGAS-STING signaling, which is the backbone of our VDAC1/ISG15-BECN1 mitophagy-block hypothesis in Arm 2. This review doesn't test our specific nodes (VDAC1, ISG15-BECN1, POLG, MFN1/2, PINK1/Parkin), but it provides independent conceptual support that the mitochondrial-dynamics-to-inflammasome pipeline we're proposing is an active, biologically plausible axis being pursued broadly in the inflammation field.

Caveats

  • This is a narrative review, not new primary data — it synthesizes existing mechanisms rather than testing SAMHD1, ANKIB1, or any A565T-specific node.
  • The diseases discussed (sepsis, neuroinflammation, osteoarthritis, cancer) are not interferonopathies, so applicability to a chronic, low-grade IFN-tone condition like SAMHD1 A565T is inferential, not demonstrated.
  • No heterozygous partial-loss-of-function genetic model is discussed; the fission/fusion-NLRP3 licensing concept is drawn from acute injury/inflammation contexts, which may differ mechanistically from a chronic, dNTP-driven state.

What to watch

The key open question this raises for our model is whether the specific "fragile mtDNA" (oxidized, ribonucleotide-containing) concept described here can be mapped onto SAMHD1 A565T cells experimentally — i.e., does the dNTP excess in Arm 3 actually generate this particular class of hyper-immunogenic mtDNA, and does correcting mitochondrial fission/fusion balance modulate NLRP3 output in patient-relevant cells?

Source: Mitochondrial dynamics and metabolic regulation in cellular inflammation: From mechanisms to precision therapeutics — 2026.

SAMHD1 Research Digest — 2026-07-18

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 35 papers evaluated | 6 high-relevance (≥7) | 17 medium (5–6) | 12 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Transition Metal Activation Reframes SAMHD1 Regulation. (from biochemistry/metalloenzyme spectroscopy)
Calderone Logan A; Gizzi Anthony; Pinninti Soumika; Stivers James T; Pandelia Ma — ACS chemical biology 2026
Score: 8/10 | Pathways: dNTPase, treatment-target

This paper directly characterizes the metal cofactor requirements (iron/manganese) for SAMHD1's dNTPase catalytic activity, providing fundamental mechanistic insight into the enzyme whose partial loss-of-function (as in A565T) drives the entire dNTP pool expansion cascade underlying this syndrome.
DOI: 10.1021/acschembio.6c00438

Mitochondrial dynamics and metabolic regulation in cellular inflammation: From mechanisms to precision therapeutics. (from Pharmacology/mitochondrial cell biology)
Park Woo Hyun — Pharmacology & therapeutics 2026
Score: 8/10 | Pathways: NLRP3, cGAS-STING, mito-dNTP-transport, nucleotide-rewiring, treatment-target, VDAC1

Directly engages ox-mtDNA/cGAS-STING/NLRP3 activation via mitochondrial dynamics and explicitly discusses the YME1L-SLC25A33 pyrimidine-imbalance axis, closely paralleling the PNC1/2 nucleotide-carrier mechanism central to the disease model.
DOI: 10.1016/j.pharmthera.2026.109086

MGMT deficiency augments STING-mediated inflammatory responses accompanied by metabolic alterations in macrophages. (from DNA repair biology / cancer genetics)
Kongkavitoon Pornrat; Boonmee Atsadang; Pattarakankul Thitiporn; Wongprom Benjaw — Scientific reports 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, other

Demonstrates that DNA repair deficiency (MGMT) amplifies STING-TBK1-IRF3 signaling and mitochondrial oxidative metabolism in macrophages, directly relevant to the interferon-mitochondrial crosstalk (cGAS-STING/IRF3, mitochondrial respiration, DNA damage) central to the SAMHD1 syndrome's BLUE/RED loops.
DOI: 10.1038/s41598-026-62431-4

The Development of UM-232, a Covalent STING Antagonist. (from Medicinal chemistry/drug discovery)
Barasa Leonard; DeOrsey Leo; O'Reilly Maeve D; Cahill Sara E; Choudhary Shruti — ACS medicinal chemistry letters 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target

Describes a novel covalent STING antagonist directly targeting the cGAS-STING axis (Loop A) that drives the IFN-I overproduction central to this SAMHD1 haploinsufficiency syndrome, offering potential therapeutic relevance despite no direct SAMHD1 data.
DOI: 10.1021/acsmedchemlett.6c00114

Electroacupuncture alleviates spinal cord injury by regulating M2-like polarization of myeloid cells through CMPK2/NLRP3 inflammasome inhibition. (from Neurology/Rehabilitation (spinal cord injury, acupuncture))
Zhang Kai; Zhang Mengru; Chen Yi; Ni Ziao; Huang Yi — International immunopharmacology 2026
Score: 7/10 | Pathways: NLRP3, mito-dNTp-transport, nucleotide-rewiring, treatment-target

This paper directly implicates CMPK2 as a regulator of NLRP3 inflammasome activation and myeloid polarization, mechanistically connecting the CMPK2-dependent mitochondrial dNTP salvage pathway (a key node in the SAMHD1/PNC1/PNC2 nucleotide-rewiring model) to NLRP3-driven neuroinflammation, offering a non-obvious cross-context validation of the CMPK2/NLRP3 axis relevant to the SAMHD1 haploinsufficiency mechanism.
DOI: 10.1016/j.intimp.2026.116989

Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction (from Cardiology)
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, POLG-mtDNA, clinical-phenotype, treatment-target

Describes mtDNA release activating cGAS-STING/TLR9 and NLRP3 inflammasome as a cross-organ inflammatory amplifier, directly paralleling the BLUE/Loop A and NLRP3 priming mechanisms in the SAMHD1 syndrome model though in a cardiology (HFpEF) context rather than SAMHD1-driven disease.
DOI: 10.3389/fimmu.2026.1866184

🟡 Medium Relevance (Score 5–6)

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

Niflumic acid suppresses NLRP3 inflammasome activation by limiting chloride efflux and mitochondrial ROS production. (from pharmacology/drug repurposing)
Li Yuanhao; Xie Qianqian; Sun Tianyin; Lu Jiwei; Li Mengmeng — Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, urate-NLRP3, treatment-target

Paper details a mitochondrial ROS-dependent NLRP3 activation mechanism (via chloride efflux/TMEM16F) and MSU-crystal-driven inflammasome activation, both directly paralleling the GOLD (urate-NLRP3) and mito-ROS-NF-kB routes in the disease model, with NFA representing a potential adjunct NLRP3-targeting therapeutic.
DOI: 10.1007/s00011-026-02328-0

Targeting CCDC90B restores intestinal stem cell function under hyperuricemic stress. (from Gastroenterology/stem cell biology)
Peng Xiuying; Li Moxuan; Zeng Kaixuan; Lv Wantong; Huang Shuai — Stem cell reports 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Demonstrates the GOLD-stream mechanism (uric acid → mitochondrial ROS → NLRP3 activation) directly, relevant to the family's SAMHD1-driven dGTP/purine catabolism route to inflammasome activation, albeit in intestinal stem cells rather than immune cells.
DOI: 10.1016/j.stemcr.2026.102970

Ring-finger protein 5 protects against diabetic kidney disease by targeting and degrading STING. (from Nephrology/Endocrinology (diabetic kidney disease))
Dong Chunping; Sun Yan; Li Hui; Qiao Yuan; Gao Shan — Pathology, research and practice 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates RNF5-mediated ubiquitin degradation of STING suppressing TBK1/IRF3/NF-kB activation and fibrosis in diabetic kidney disease, offering a plausible downstream therapeutic node for the STING/NF-kB arm of the interferon-mitochondrial syndrome despite being in a different clinical context (nephrology/diabetes).
DOI: 10.1016/j.prp.2026.156618

Targeting MDA5-Mediated Interferon Responses in Type 1 Diabetes: Structural Insights, Mechanism, and Potential Therapeutic Approaches. (from Endocrinology (type 1 diabetes autoimmunity))
Iwaloye Opeoluwa F; Mathews Clayton E; Li Danmeng — Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2026
Score: 6/10 | Pathways: IRF7-metabolic, NF-kB-IKK, treatment-target, clinical-phenotype

MDA5/IFIH1-driven type I interferon signaling via TBK1/IKKε-IRF and NF-κB converges mechanistically with the SAMHD1 cGAS-STING/NF-κB interferonopathy axis and shares therapeutic logic (JAK/IFN pathway targeting) relevant to autoimmune comorbidities in the family phenotype spectrum.
DOI: 10.1177/10799907261467555

Senegenin mitigates neuroinflammation, pyroptosis, and apoptosis in cerebral ischemia via inhibiting STING and downstream inflammatory pathway. (from neurology/stroke pharmacology)
Chauhan Chandan; Kaundal Ravinder K — European journal of pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, treatment-target

Demonstrates pharmacological STING-TBK1-IRF3 and NF-κB/NLRP3 pathway inhibition reducing pyroptosis/apoptosis in a disease model, directly relevant to the core Loop A/B mechanism though in an unrelated ischemic stroke context rather than SAMHD1-driven interferonopathy.
DOI: 10.1016/j.ejphar.2026.179147

Dietary riboflavin blocks the cGAS-STING pathway to curb hypoxia-induced hepatic inflammation in sub-adult grass carp (Ctenopharyngodon idella). (from veterinary/aquaculture nutrition science)
Zhong Lin; Feng Lin; Wu Pei; Jiang Weidan; Zhang Hongyun — Animal nutrition (Zhongguo xu mu shou yi xue hui) 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

This fish study demonstrates VDAC1/mtDNA-driven cGAS-STING-TBK1-IRF3/NF-kB (p-P65) activation causing hepatic inflammation under hypoxia, mirroring the BLUE loop and NF-kB crosstalk mechanisms in the SAMHD1 syndrome, with riboflavin as a mitochondrial-protective therapeutic lever relevant to treatment strategies.
DOI: 10.1016/j.aninu.2026.01.012

Reduced myocardial NRG-1/ErbB4 signaling is associated with STING-linked macrophage pyroptotic signaling in sepsis-induced cardiac injury. (from Cardiology/sepsis)
Wei Yanian; Wang QianWen; Shen Cheng; Pan Xia; Kang Wen — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, treatment-target

This paper demonstrates cGAS-STING-TBK1-IRF3/NF-kB signaling driving macrophage pyroptosis (NLRP3, caspase-1, GSDMD-N) in cardiac injury, directly relevant to the interferon-inflammasome axis and cardiac phenotype seen in the SAMHD1 family, though it lacks any SAMHD1 connection.
DOI: 10.1016/j.intimp.2026.117044

LKB1/ AMPK deficiency aggravates mitochondrial DNA leakage via mTOR-dependent mitophagy damage in liver injury sensitized by trichloroethylene. (from Occupational/environmental toxicology and hepatology)
Zhu Lifu; Wan Chenghuan; Li Zijun; Fan Xuan; Liu Dongsheng — 2026
Score: 6/10 | Pathways: cGAS-STING, mTOR-lysosomal, treatment-target

Demonstrates mitophagy failure leading to mtDNA leakage and cGAS-STING-driven inflammation via LKB1/AMPK/mTOR axis, mechanistically parallel to the mitochondrial-interferon convergence in the SAMHD1 syndrome despite a different toxicological trigger.
DOI: 10.1016/j.cbi.2026.112261

Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation. (from Neurodegeneration/neuroimmunology)
Zou Mingyue; Zhao Tengyu; Wu Weidong; Zhang Jian; Pan Pengyu — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, ISG15-mitophagy, mTOR-lysosomal, treatment-target

Reviews microglial mitophagy failure driving mtDNA/mtROS-triggered cGAS-STING and NLRP3 activation with TBK1 signaling, mechanistically parallel to the mitochondrial-quality-control/interferon-inflammasome axis central to the SAMHD1 syndrome, though disease context is Alzheimer's rather than SAMHD1.
DOI: 10.1186/s12974-026-03946-5

The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart (from Cardio-oncology/pharmacology)
Kelsey H. Fisher-Wellman; Richard D. Lutze; Logan G. Kirkland; J. Beak; Mansi Go — Science Advances 2026
Score: 6/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial DNA damage triggering cGAS-STING innate immune activation via mitochondrial dysfunction and ETC impairment, directly paralleling the BLUE/Loop A mechanism in the SAMHD1 syndrome, though in a drug-cardiotoxicity rather than SAMHD1 context.
DOI: 10.1126/sciadv.aeb2695

The mitochondrial logic of inflammaging: how energy imbalance drives fibroblast SASP and tissue-specific aging (from Geroscience/periodontology)
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

This paper reviews mitochondrial danger signal (mtROS/mtDNA)-driven cGAS-STING/NLRP3/NF-kB convergence in cellular senescence, mechanistically paralleling the SAMHD1 syndrome's Loop A/B and NF-kB crosstalk axes though in a general aging/periodontal context without SAMHD1 involvement.
DOI: 10.3389/fimmu.2026.1881243

How Redox Modulation May Help Prevent Age-Related Decline (from nutrition/geroscience)
M. Amirova — PHYTONutrients 2026
Score: 6/10 | Pathways: NLRP3, cGAS-STING, NF-kB-IKK, NF-kB-NLRP3-priming, mito-ROS-NF-kB, treatment-target

General review of mitochondrial DAMP-driven cGAS-STING/NLRP3/NF-kB inflammaging and NRF2 antioxidant modulation overlaps mechanistically with the IFN-mitochondrial-inflammasome axis but lacks SAMHD1-specific or dNTP pathway data.
DOI: 10.62368/pn.v5i1.71

Biallelic mutations in SUPV3L1 cause a variable leukodystrophy due to impaired mitochondrial degradosome function (from Neurology/leukodystrophy genetics)
L. Green; Noémie Hamilton; M. Elpidorou; R. Maroofian; Maha S. Zaki — Research Square 2026
Score: 6/10 | Pathways: cGAS-STING, AGS-spectrum, clinical-phenotype

Mitochondrial dsRNA degradosome dysfunction driving type I interferon activation via microglia parallels the SAMHD1-driven mitochondrial-to-interferon signaling axis, though it operates through a distinct RNA-sensing (rather than dNTPase/cGAS-mtDNA) mechanism within the broader interferonopathy spectrum.
DOI: 10.21203/rs.3.rs-4356120/v2

A Multi-Center Integrative Cohort Characterizing the Genetic, Clinical, and Transcriptomic Features of ACP5 Deficiency. (from Rheumatology/genetics (skeletal dysplasia and immune dysregulation))
Zhong Shiling; Ma Shuangyue; El Chazli Yasmine; Zheng Jika; Sun Xiangwei — Arthritis & rheumatology (Hoboken, N.J.) 2026
Score: 5/10 | Pathways: JAK-STAT, NF-kB-IKK, AGS-spectrum, clinical-phenotype, treatment-target

ACP5/SPENCDI is a distinct interferonopathy with overlapping type I IFN, NF-κB, and JAK-STAT signaling and JAK inhibitor treatment response, offering mechanistic and therapeutic parallels to the SAMHD1 interferonopathy spectrum despite being a different causal gene.
DOI: 10.1002/art.70279

Leveraging Mitochondria-Endoplasmic Reticulum Functional Interplay With an On-Demand Nanoparticle to Boost mtDNA-Based STING Immunotherapy. (from Oncology/nanomedicine)
Chen Han; Qu Haijing; Pan Yuqing; Cheng Wei; Wu Jie — Advanced materials (Deerfield Beach, Fla.) 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target

This paper explores mtDNA-driven cGAS-STING activation via a mitochondria-ER nanoparticle system for cancer immunotherapy, which is mechanistically relevant to the BLUE pathway's mtDNA-cGAS-STING axis but oncology-focused rather than SAMHD1-related.
DOI: 10.1002/adma.74146

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

Uses prime editing to engineer epitope-shielded CD34+ HSPCs for toxin-free conditioning, representing a relevant myeloid/HSC gene correction delivery advance analogous to strategies that could correct SAMHD1 missense variants, though disease context (beta-thalassemia) is unrelated to interferonopathy pathways.
DOI: 10.64898/2026.07.07.736903

Base Editing Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of X-Linked Severe Combined Immunodeficiency (from Gene therapy/immunodeficiency)
S. de Ravin; Michelle Ma; Yuzhi Yin; Siyuan Liu; Andrés Zea Vera — Journal of Human Immunity 2026
Score: 5/10 | Pathways: gene-therapy-delivery

Demonstrates base-editing correction of a het/hemizygous immune gene mutation (IL2RG) in HSPCs, relevant as a translational precedent for future SAMHD1 A565T correction strategies but not mechanistically tied to the interferon-mitochondrial-NLRP3 axis.
DOI: 10.70962/pidtc2026abstract.4

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Annual gout flare frequency as a marker of sustained cardiovascular risk: a clinical threshold for risk stratification. (from Rheumatology/Cardiology)
Tung Kuei-Ting; Chen Solomon Chih-Cheng; Lee Chun — Rheumatology (Oxford, England) 2026
Score: 4/10 | Pathways: urate-NLRP3, clinical-phenotype

This clinical epidemiology paper links gout flare frequency to cardiovascular risk via cumulative inflammatory burden, tangentially relevant to the GOLD pathway (dGTP-uric acid-MSU crystal-NLRP3 axis) but does not address SAMHD1, interferon, or mitochondrial mechanisms directly.
DOI: 10.1093/rheumatology/keag370

Approach to the patient with APS-1/APECED. (from Endocrinology)
Webb Taura; Pechacek Joseph; Lionakis Michail S — The Journal of clinical endocrinology and metabolism 2026
Score: 4/10 | Pathways: JAK-STAT, clinical-phenotype, other

APS-1/AIRE is a distinct monogenic autoimmune tolerance disorder with IFN-gamma-driven pathology and JAK inhibitor treatment rationale, offering only loose conceptual parallel (JAKi as interferonopathy therapy) but no direct SAMHD1/cGAS-STING/NLRP3 mechanistic overlap.
DOI: 10.1210/clinem/dgag282

MDA5 and the integrated stress response control sex-specific type 1 diabetes onset in NOD mice. (from Endocrinology/diabetes autoimmunity)
Van Dis Erik; DeGidio Alessandra T; Yao Lara; Winship Damion; Sidrauski Carmela — bioRxiv : the preprint server for biology 2026
Score: 4/10 | Pathways: AGS-spectrum, other

This paper links MDA5/IFIH1 and integrated stress response to autoimmune diabetes in the AGS-adjacent RNA-sensing innate immune context, offering tangential mechanistic overlap (nucleic acid sensing driving type I IFN-like pathology) but no direct SAMHD1, cGAS-STING, NLRP3, or mitochondrial dNTP connection.
DOI: 10.64898/2026.07.02.736190

Compound delivery of eVLPs enhances prime editing for targeted genome engineering and high-throughput screening. (from functional genomics/gene editing technology)
Langley Jethro; Baudrier Lou; Curry Jada; Narta Kiran; Todesco Hayley M — Cell genomics 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General-purpose eVLP/prime-editing methods advance is technically relevant to future SAMHD1 correction strategies but not targeted to immune/myeloid cells or the disease mechanism itself.
DOI: 10.1016/j.xgen.2026.101302

Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7. (from neurology/gene therapy (Alzheimer's disease))
Kim Yunkyung; Lee Gaeun; An Saemin; Park Hanseul; Kim Hongwon — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates PE7 prime editing technology for allele-specific correction (APOE4→APOE3) in neurons, offering a technical precedent for correcting heterozygous missense variants like SAMHD1 A565T, but is otherwise unrelated to interferonopathy/SAMHD1 biology or immune cell targeting.
DOI: 10.1002/advs.76658

SARS-CoV-2 ORF9b exploits mitochondrial recruitment to TOMM70 for proteasomal protection and tunes inflammatory remodeling during lung infection (from Virology/Structural Biology)
Yining Zhao; Lauriane Kergoat; Guilherme Dias de Melo; F. Larrous; Guillaume Dru — bioRxiv 2026
Score: 4/10 | Pathways: cGAS-STING, other

This paper explores SARS-CoV-2 ORF9b-mitochondrial (TOMM70) interactions and inflammatory remodeling via a Complex IV subunit substitute, touching on mitochondrial-innate immune crosstalk and interferon regulation but without direct SAMHD1, cGAS-STING, or NLRP3 pathway involvement relevant to the described syndrome.
DOI: 10.64898/2026.07.13.738231

Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives (from biomedical engineering/nanomedicine)
Meijia Yang; Yiqiong Song; Ziyang Wang; Ke Chao; Lifeng Li — MedComm 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General review of genome editing delivery platforms with no SAMHD1-specific or immune/myeloid cell targeting focus, only tangentially relevant as background for future gene correction strategies.
DOI: 10.1002/mco2.70791

Proteomics-based characterization of apigenin-mediated anti-inflammatory effects in TNF-α-stimulated ARPE-19 cells. (from Ophthalmology/pharmacology (flavonoid anti-inflammatory research in retinal disease))
Chen Xi; Liao Meilin; Han Ruifang; Gao Juan; Lu Ping — International immunopharmacology 2026
Score: 3/10 | Pathways: NF-kB-IKK, JAK-STAT, ISG15-mitophagy

This paper studies apigenin's suppression of NF-κB/MAPK signaling and interferon-stimulated proteins (STAT1, ISG15, OAS3, IFIT3) in retinal pigment epithelial cells, touching peripheral pathway nodes (NF-κB, ISG15, IFN-related proteins) relevant to the syndrome's mechanism but with no SAMHD1, mitochondrial, or NLRP3 connection and an unrelated ophthalmologic/pharmacologic context.
DOI: 10.1016/j.intimp.2026.117048

Guiqi Baizhu prescription attenuates 5-FU-induced intestinal mucositis by targeting IKKβ to inhibit M1 macrophage polarization. (from Gastroenterology/Traditional Chinese Medicine oncology supportive care)
Zhou Yu-Cen; Li Ya-Ling; Ma Jing; Li Junjie; Si Qi — Chinese medicine 2026
Score: 3/10 | Pathways: NF-kB-IKK

Paper focuses on IKKβ/NF-κB inhibition in a traditional Chinese medicine model of chemotherapy-induced gut mucositis, only tangentially touching the NF-κB-IKK axis without connection to SAMHD1, interferonopathy, or mitochondrial mechanisms.
DOI: 10.1186/s13020-026-01406-z

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

General review of nanomaterial delivery platforms for CRISPR/base/prime editing with no SAMHD1, immune cell, or mitochondrial-interferon pathway specificity.
DOI: 10.3390/ijms27135988

Intelligent metal-integrated hydrogels orchestrate pyroptosis and cGAS-STING for potentiated treatment of colorectal cancer peritoneal metastasis. (from Oncology/biomaterials drug delivery)
Zhang Lin-Zhu; Si Liang-Wei; Xu Hui; Xiong Fei; Qin Juan — 2026
Score: 3/10 | Pathways: cGAS-STING, other

Describes cGAS-STING activation via mtDNA/pyroptosis in a cancer-therapeutic (hydrogel/cobalt) context unrelated to SAMHD1 mechanism or family phenotypes, though it touches the same signaling node.
DOI: 10.1016/j.jconrel.2026.115184

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

This review covers gut microbiota-mitochondria-immune crosstalk (cGAS-STING/NLRP3, mtDNA, mitophagy) in gynecological disease but is not connected to SAMHD1, dNTP metabolism, or the family phenotype spectrum.
DOI: 10.3389/frph.2026.1845581

Pathway Coverage This Week

  • treatment-target: 20 papers
  • cGAS-STING: 18 papers
  • NLRP3: 11 papers
  • NF-kB-IKK: 11 papers
  • other: 6 papers
  • clinical-phenotype: 6 papers
  • gene-therapy-delivery: 6 papers
  • mito-ROS-NF-kB: 5 papers
  • prime-editing: 5 papers
  • urate-NLRP3: 3 papers
  • AGS-spectrum: 3 papers
  • JAK-STAT: 3 papers
  • nucleotide-rewiring: 2 papers
  • VDAC1: 2 papers
  • NF-kB-NLRP3-priming: 2 papers
  • mTOR-lysosomal: 2 papers
  • ISG15-mitophagy: 2 papers
  • dNTPase: 1 papers
  • mito-dNTP-transport: 1 papers
  • mito-dNTp-transport: 1 papers
  • POLG-mtDNA: 1 papers
  • IRF7-metabolic: 1 papers

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 SVPLA<sub>2</sub> 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