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VDAC1

SAMHD1 Research Digest — 2026-09-13

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 29 papers evaluated | 6 high-relevance (≥7) | 12 medium (5–6) | 11 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses (from cell biology/organelle biology review)
Zhuo-Er Li; Chunli Wang; Jin-Rong Zhang; Zhi-Qiang Guo — Frontiers in Immunology 2026
Score: 8/10 | Pathways: ISG15-mitophagy, cGAS-STING, JAK-STAT, treatment-target

This review directly addresses the RED pathway mechanism (ISG15/ISGylation of MFN1/MFN2 blocking mitophagy) that is central to the SAMHD1 A565T mitochondrial-interferon convergence model, including STING and mitophagy crosstalk relevant to disease pathogenesis.
DOI: 10.3389/fimmu.2026.1960492

Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation. (from Cell biology/mitochondrial trafficking)
— Cell reports 2026
Score: 7/10** | Pathways: cGAS-STING, treatment-target

Identifies a novel mitochondria-lysosome trafficking axis (Fis1-TBC1D15-Rab7A) controlling STING degradation and signal termination, directly relevant to the chronic/unresolved IFN-I signaling (Loop A/RED) implicated in the SAMHD1 A565T interferonopathy.
DOI: 10.1016/j.celrep.2026.117994

Precision tuning of STING signaling: a mutational blueprint (from structural biology / high-throughput functional genomics)
— Signal Transduction and Targeted Therapy 2026
Score: 7/10** | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This comprehensive mutational atlas of STING signaling directly maps the structural determinants of IFN-I induction and NF-κB activation downstream of cGAS-STING, a core pathway (BLUE stream) driving the interferon-mitochondrial syndrome in SAMHD1 A565T haploinsufficiency, and offers therapeutic modulation insights applicable to future STING antagonist strategies for this family.
DOI: 10.1038/s41392-026-02968-y

Mitochondria-Targeted Multimodal Nanotherapeutics Suppress Oxidized mtDNA-Driven Inflammation at the Source. (from Nanomedicine/pulmonology (ARDS))
Li Wen-Ling; Cao Juan; Wang Yu-Lin; Fan Yu-Han; Xu Jia-Qi — 2026
Score: 7/10 | Pathways: VDAC1, NLRP3, treatment-target, POLG-mtDNA

This nanotherapeutic directly targets oxidized mtDNA leakage and downstream inflammation at the mitochondrial source, a core mechanism (Loop A/B) in SAMHD1 A565T pathology, offering a plausible therapeutic strategy analogous to VBIT-4/MCC950 for the interferon-mitochondrial syndrome.
DOI: 10.1002/advs.77577

Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOS (from Reproductive endocrinology/gynecology (PCOS))
— Cell Death Discovery 2026
Score: 7/10** | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, clinical-phenotype

Demonstrates mPTP-mediated mtDNA release activating cGAS-STING-NF-κB inflammatory cascade, directly paralleling the BLUE-loop/NF-κB crosstalk mechanism central to the SAMHD1 interferon-mitochondrial model, with therapeutic parallels (STING/ER stress inhibitors, melatonin) relevant to treatment translation.
DOI: 10.1038/s41420-026-03339-w

Mitochondria in SARS-CoV-2 infection: Immune interactions and molecular approaches in the Post COVID-19 condition. (from Virology/Post-viral syndrome (Post-COVID condition))
Barros Maria Clara; Souza Felipe Gouvêa de; Costalat Helenize; Pinho Catarina To — 2026
Score: 7/10 | Pathways: NLRP3, mito-ROS-NF-kB, ISG15-mitophagy, ME-CFS, clinical-phenotype

This review covers SARS-CoV-2-induced mitochondrial dysfunction, ROS-driven NLRP3 activation, mitophagy impairment, and post-COVID sequelae, directly paralleling the proband's viral-triggered ME/CFS and the interferon-mitochondrial convergence mechanism central to the SAMHD1 A565T phenotype.
DOI: 10.1590/1678-4685-gmb-2025-0118

🟡 Medium Relevance (Score 5–6)

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

The interaction between HIV-1 central polypurine tract and host SAMHD1 dNTPase during HIV-1 vector transduction in human primary nondividing monocyte-derived macrophages. (from Virology/gene therapy vector engineering)
Alvarez Natalie N; Burke Hannah S; Freeman Tzipporah; Taki Sara; Li Qun — Virus genes 2026
Score: 6/10 | Pathways: dNTPase, treatment-target

Directly studies SAMHD1 dNTPase activity and Vpx-mediated degradation in macrophages, providing mechanistic insight into the core dNTP pool pathway relevant to A565T haploinsufficiency, though focused on viral restriction/vector transduction rather than the interferonopathy phenotype.
DOI: 10.1007/s11262-026-02272-5

Redox-driven mitochondrial DNA stress in hepatocellular carcinoma: innate immune remodelling, tumour immune escape, and immunotherapy implications (from Hepatology/Oncology)
Ze Chang; Guan-Nan Liu; Jin-Shan Zhang; Hai-Lin Lei; Hai-Yan Quan — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

Paper details mtDNA release mechanisms (oxidation, cGAS-STING, TLR9, NLRP3/TFAM coupling) directly parallel to the BLUE/PURPLE loops in the SAMHD1 mechanism, though in an HCC oncology context rather than SAMHD1 haploinsufficiency.
DOI: 10.3389/fimmu.2026.1903643

Colchicine-related effects on gene and protein expression in gout. (from Rheumatology)
Mitchell Will T; Wheeler Austin M — Current opinion in rheumatology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Colchicine's mechanism via NLRP3 inhibition and MSU-driven inflammation directly overlaps with the GOLD pathway (dGTP→uric acid→MSU crystals→NLRP3) and offers a potential treatment lead relevant to the SAMHD1 A565T inflammasome hyperactivation phenotype.
DOI: 10.1097/BOR.0000000000001192

Mitochondrial Transplantation Suppresses mtDNA-cGAS/STING-Mediated Innate Immunity by Enhancing PINK1/Parkin-Dependent Mitophagy to Attenuate Keloid Fibrosis (from dermatology/plastic surgery (keloid fibrosis))
Wen-Jing Wang; Yuan-Bo Liu; Ji-Peng Song; Zou-Zou Yu; Zi-Xian Chen — Antioxidants 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target

Demonstrates mtDNA leakage driving cGAS/STING activation via impaired PINK1/Parkin mitophagy in fibrosis, directly paralleling the BLUE/RED loops of SAMHD1-related interferonopathy though in a dermatologic keloid model rather than SAMHD1 haploinsufficiency.
DOI: 10.3390/antiox15091120

Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration. (from neurology/neurodegeneration)
Basak Bishal; Riley Julia F; Nataraj Neha M; Holzbaur Erika Lf — 2026
Score: 6/10 | Pathways: ISG15-mitophagy, NF-kB-IKK, treatment-target, other

Reviews PINK1/Parkin mitophagy pathways and their links to NF-κB and cGAS-STING neuroinflammation, directly relevant to the RED loop mitophagy block and neuroinflammatory mechanisms in the SAMHD1 model though not SAMHD1-specific.
DOI: 10.1172/jci199847

STC1 promotes monosodium urate crystal-induced gouty inflammation via the cAMP-PKA-NF-κB/NLRP3 pathway in mice. (from Rheumatology (gouty arthritis))
He Yue; Zheng Hui; Yue Zhi; Ge Tingqiu; Hu Yanqing — Cellular signalling 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, NF-kB-NLRP3-priming, mito-ROS-NF-kB

Demonstrates MSU crystal-driven NLRP3/NF-κB inflammasome activation via cAMP-PKA and mitochondrial ROS, directly paralleling the GOLD (urate-NLRP3) and mito-ROS-NF-κB axes implicated in SAMHD1 dGTP-driven purine catabolism pathology, though not SAMHD1-specific.
DOI: 10.1016/j.cellsig.2026.112862

Genomic Structural Equation Modeling Identifies a Shared Inflammatory Genetic Dimension Across Inflammatory Arthritis Phenotypes and Biomarkers. (from statistical genetics/rheumatology)
Feng Xiaojian; Pan Zhixian; Liu Guoping — Annals of human genetics 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, clinical-phenotype, NF-kB-NLRP3-priming

This genomic SEM study converges on NLRP3, urate, and IL6R pathways underlying rheumatoid arthritis, psoriatic arthritis, and gout, directly paralleling the GOLD-stream uric acid/NLRP3 axis and RA/PsA phenotypes documented in the SAMHD1 family.
DOI: 10.1111/ahg.70058

The Secretome Derived From Human Umbilical Cord Mesenchymal Stem Cells Improves Skin Photoaging by Enhancing Mitophagy to Inhibit the cGAS-STING Pathway. (from Dermatology/regenerative medicine (stem cell secretome therapy))
Tang Tingting; Lin Meifen; Yang Jingjing; Yang Xinyu; Xu Xunhong — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target

Demonstrates mitophagy-mediated suppression of mtDNA leakage and cGAS-STING/IFN-β activation, directly relevant to the BLUE/RED mechanistic loops in SAMHD1 haploinsufficiency though applied to a dermatologic aging model rather than SAMHD1 itself.
DOI: 10.1111/acel.70701

The GPX3-VCAM1 Axis Gates Pro-Fibrotic Tubule Cell Fate in Hyperuricemic Nephropathy. (from Nephrology)
Qi Yunfei; Zhao Qiang; Lve Yue; Yuan Yaming; Zhou Tingting — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Demonstrates soluble uric acid activating renal NLRP3 inflammasome to drive fibrosis, paralleling the GOLD dGTP-to-uric-acid-to-NLRP3 pathway in the SAMHD1 mechanism, though in a distinct hyperuricemic nephropathy context without SAMHD1 involvement.
DOI: 10.1002/advs.77676

The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses. (from Oncology/Virology)
Guo Limei; Li Li; Wang Fang; Liu Wen; Zhang Yan — 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target

General review of cGAS-STING pathway in oncogenic virus-driven cancers provides background on the core BLUE-loop signaling axis but has no direct connection to SAMHD1, mitochondrial dNTP dysregulation, or the described family phenotype.
DOI: 10.1002/cbf.70296

Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation. (from Oncology (cancer immunotherapy/redox biology))
Deng Xiaoyi; Deng Zaidong; Zhu Bin; Hu Ruiqi; Ma Jing — 2026
Score: 5/10 | Pathways: cGAS-STING, other

Demonstrates mitochondrial DNA release triggering cGAS-STING via oxidative/mitochondrial stress in cancer cells, a mechanism parallel to the BLUE loop in SAMHD1 pathology though in an oncology/ferroptosis context rather than SAMHD1 haploinsufficiency.
DOI: 10.1186/s13045-026-01840-4

Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems. (from gene therapy / RNA delivery engineering)
Lei Xinlin; Chen Didi; Zhang Kun; Liu Xiyu; Chen Qiubing — Nature biomedical engineering 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a generalizable LNP/pegRNA delivery advance for in vivo prime editing that is relevant as a future therapeutic correction strategy for a heterozygous missense variant like SAMHD1 p.A565T, though it demonstrates only liver hepatocyte editing rather than immune/myeloid cells.
DOI: 10.1038/s41551-026-01787-4

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Navigating off-target effects in CRISPR-based genome editing for safer gene therapies (from genome editing / gene therapy engineering)
— Discover Genetics and Evolution 2026
Score: 4/10** | Pathways: prime-editing, gene-therapy-delivery

General CRISPR off-target review relevant to future gene correction strategies for SAMHD1 variants but lacks disease-specific or pathway-specific content.
DOI: 10.1007/s00294-026-01339-y

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2 (from gene editing / genomics methodology)
Tingting Cong; Run-Da Xu; Xuan-Cheng Chen; Jun-Song Yuan; Zuo-Miao 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 missense variants like A565T, but has no direct connection to SAMHD1 biology or the interferon-mitochondrial pathway.
DOI: 10.1038/s41467-026-76778-9

Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts (from virology/biochemistry of mitochondrial signaling)
Nao Morimoto; Tomohiko Okazaki — Frontiers in Physiology 2026
Score: 4/10 | Pathways: cGAS-STING, other

MAVS/RLR pathway is a parallel mitochondrial-innate immune signaling axis distinct from but conceptually adjacent to the cGAS-STING/IFN-I pathway central to SAMHD1 interferonopathy, without direct SAMHD1 or NLRP3/VDAC1/ISG15 mechanistic overlap.
DOI: 10.3389/fphys.2026.1907325

Itaconate and its derivatives in human health and diseases. (from immunometabolism)
Gu Jianyou; Zhang Wenying; Zhang Junfeng; Zeng Silue; Xia Renpei — 2026
Score: 3/10 | Pathways: NLRP3, other

This is a general review of itaconate/IRG1-ACOD1 immunometabolism with tangential relevance to NLRP3-driven inflammation but no direct connection to SAMHD1, dNTPase, cGAS-STING, or mitochondrial dNTP transport pathways central to this disease.
DOI: 10.1038/s41392-026-02936-6

Tumor microenvironment and signaling pathways in melanoma brain metastasis. (from Oncology/neuro-oncology)
Rosell Rafael; González-Cao María; Olmo-González Daniel; Hold Emilia; Molina-Vil — Annals of translational medicine 2026
Score: 3/10 | Pathways: cGAS-STING, other

This melanoma brain metastasis review touches on cGAS-STING/TBK1 and mitochondrial dysfunction mechanisms but is focused on oncology/tumor microenvironment unrelated to SAMHD1 A565T pathophysiology.
DOI: 10.21037/atm-2026-0127

Context-dependent roles of cGAS-STING signaling in glioblastoma: Therapeutic resistance, drug delivery, and heterogeneity-informed translation. (from Neuro-oncology)
— Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 3/10** | Pathways: cGAS-STING, NF-kB-IKK

This is a glioblastoma-focused oncology review discussing cGAS-STING/NF-kB signaling in tumor context, with no direct connection to SAMHD1, its mechanistic pathways, or the family phenotype spectrum.
DOI: 10.1016/j.biopha.2026.119915

Elucidate the structural role of helper lipids in modulating hepatic expression following repeated intravenous administration of mRNA-LNPs (from pharmaceutical sciences/nanomedicine drug delivery)
Jia-Hao Ge; Xiaochen Bo; Xinye Zhu; M. Long; Yi-Qing Zhang — Materials Today Bio 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper concerns mRNA-LNP formulation for hepatic protein delivery and gene editing, with only tangential relevance via IL-6/inflammation induction by lipid components, not directly connected to SAMHD1 or the core interferon-mitochondrial pathways.
DOI: 10.1016/j.mtbio.2026.103621

Twelve Japanese patients with POLG-related disorders: Population-specific genetic differences of POLG variants in Japan and Europe. (from Clinical genetics/mitochondrial medicine (pediatric neurology))
Ueda Nahoko Katayama; Mimaki Masakazu; Wang Zhaoxia; Mizuno Yoko; Namai Yoshiyuk — Brain & development 2026
Score: 3/10 | Pathways: POLG-mtDNA

This paper concerns POLG mutation epidemiology in classic mitochondrial disease (PEO, mtDNA deletions) in Japanese patients, not related to SAMHD1 pathway or interferon-mitochondrial crosstalk, though POLG stalling is a downstream node in the PURPLE loop.
DOI: 10.1016/j.braindev.2026.104590

Factors associated with hyperuricemia in overweight or obese adults of Shenzhen, China. (from Epidemiology/Endocrinology)
Tang Leyao; Dai Wenjie; Xiong Ni; Liang Liping; Wu Xin Yin — 2026
Score: 3/10 | Pathways: urate-NLRP3

This is a population epidemiology study on hyperuricemia risk factors in obesity unrelated to SAMHD1 mechanisms, only tangentially touching the GOLD pathway (dGTP→uric acid→NLRP3) via urate biology without any mechanistic or genetic link.
DOI: 10.1038/s41598-026-68519-1

Autoimmunity: Molecular Mechanisms, Biomarkers, and Therapeutic Opportunities. (from General rheumatology/autoimmunity review)
Kuang Jialong; Zhu Yin; Xu Fang; Liu Yongjing; Li Yuan — 2026
Score: 3/10 | Pathways: JAK-STAT, treatment-target, other

This is a broad general review of autoimmune disease mechanisms (immunometabolism, epigenetics, RNA regulation) without any specific mention of SAMHD1, cGAS-STING, NLRP3, interferonopathy, or mitochondrial dNTP pathways central to the SAMHD1 A565T syndrome.
DOI: 10.1002/mco2.70905

WEAK IMMUNITY DURING INSOMNIA (from Sleep medicine)
— Special journal of the Medical Academy and other Life Sciences 2026
Score: 3/10** | Pathways: ME-CFS, clinical-phenotype

This low-quality, non-peer-reviewed-looking survey on insomnia and immunity mentions mitochondrial dysfunction and ME/CFS tangentially but provides no mechanistic data on SAMHD1, interferon, or inflammasome pathways relevant to the family syndrome.
DOI: 10.58676/sjmas.v4i8.190

Pathway Coverage This Week

  • treatment-target: 14 papers
  • cGAS-STING: 12 papers
  • NLRP3: 8 papers
  • other: 6 papers
  • ISG15-mitophagy: 5 papers
  • urate-NLRP3: 5 papers
  • NF-kB-IKK: 4 papers
  • clinical-phenotype: 4 papers
  • gene-therapy-delivery: 4 papers
  • mito-ROS-NF-kB: 3 papers
  • prime-editing: 3 papers
  • JAK-STAT: 2 papers
  • POLG-mtDNA: 2 papers
  • ME-CFS: 2 papers
  • NF-kB-NLRP3-priming: 2 papers
  • VDAC1: 1 papers
  • dNTPase: 1 papers

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

SAMHD1 Research Digest — 2026-09-06

Generated by samhd1_monitor | Model: claude-sonnet-5

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

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery (from RNA epigenetics/molecular virology)
Hu Qing; Zhang Yifei; Wang Shixuan; Zeng Xueping; Wang Fengyu — preprint (preprint) 2026
Score: 7/10 | Pathways: VDAC1, cGAS-STING, NLRP3, treatment-target

This paper details VDAC1-mediated mitochondrial nucleic acid (mtRNA) extrusion activating cytosolic PRRs (RIG-I/MDA5/TLR/PKR), directly extending the BLUE-loop VDAC1-macropore mechanism central to SAMHD1 A565T interferon pathology beyond mtDNA to mtRNA, with m6A machinery as a novel druggable node.
DOI: 10.64898/2026.08.27.747681

Neonatal Aicardi-Goutières syndrome presenting with macrophage activation syndrome-like hyperinflammation and severe congenital glaucoma: a case report. (from pediatric rheumatology/neonatology and ophthalmology)
Konak Murat; Bozkurt Banu; Ceylaner Gülay; Cüceoğlu Müşerref Kasap; Özdemir Fati — Pediatric rheumatology online journal 2026
Score: 7/10 | Pathways: AGS-spectrum, JAK-STAT, treatment-target, clinical-phenotype

AGS type 2 case with type I interferonopathy responding to JAK1/2 inhibitor (ruxolitinib) directly parallels the SAMHD1 interferonopathy spectrum, MAS-like hyperinflammation, and glaucoma phenotype tracked in the family, plus congenital glaucoma overlaps with a listed family phenotype.
DOI: 10.1186/s12969-026-01264-x

🟡 Medium Relevance (Score 5–6)

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

Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure. (from cardiology/aging biology)
Bubb Kristina; Rigoni Giovanni; Papadea Polyxeni; Pironti Gianluigi; Misic Jelen — Science advances 2026
Score: 6/10 | Pathways: POLG-mtDNA, mito-ROS-NF-kB, clinical-phenotype

Demonstrates that cardiomyocyte-intrinsic POLG-driven mtDNA mutations trigger an immune/antigen-presentation response and progressive heart failure, paralleling the PURPLE-stream POLG stalling→ox-mtDNA→immune activation mechanism and supporting cardiac relevance of mitochondrial-immune crosstalk in the SAMHD1 model.
DOI: 10.1126/sciadv.aec8606

Beyond genes: EpiSwitch® and Orion platform-powered 3D genome architecture biomarkers reveal shared biology across ME/CFS, long COVID, PTSD, rheumatoid arthritis, and multiple sclerosis. (from systems genomics/epigenetics (3D chromatin architecture biomarker platform) applied across rheumatology, neurology, and post-viral fatigue syndromes)
Hunter Ewan; Alshaker Heba; Vugrinec Dominik; Bautista Shekinah; Gebregzabhar Ab — Journal of translational medicine 2026
Score: 6/10 | Pathways: ME-CFS, cGAS-STING, mTOR-lysosomal, JAK-STAT, clinical-phenotype

This paper identifies shared immune/interferon/mitochondrial/mTOR pathway convergence across ME/CFS, long COVID, RA, and MS using 3D genomic architecture analysis, directly relevant to the proband's ME/CFS phenotype and the family's autoimmune/interferonopathy features (RA tracked in family phenotypes) even though SAMHD1 is not mentioned.
DOI: 10.1186/s12967-026-08874-9

Modulatory effects of methyl gallate on the inflammatory response in gout arthritis via P2X7 receptor. (from Pharmacology/Rheumatology)
Pereira Felipe M S; Correa Luana B; Seito Leonardo N; Ranke Natalia L VON; Mende — Anais da Academia Brasileira de Ciencias 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

This paper directly addresses the GOLD pathway (dGTP→purine catabolism→uric acid→MSU crystals→NLRP3) via P2X7-mediated MSU/NLRP3 activation and IL-1β release, offering a treatment target relevant to the gout phenotype tracked in the family.
DOI: 10.1590/0001-3765202620250722

Mitochondrial immunometabolism in sepsis: bridging immune cell dysfunction and organ failure. (from Critical care/sepsis immunometabolism)
Zhang Xingzhan; Zhao Ling; Fu Wei; Pan Lili; Wu Huanhuan — Frontiers in immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

Reviews mtDNA/mtROS/cardiolipin-driven cGAS-STING and NLRP3 activation as core drivers of sepsis organ failure, mechanistically overlapping with the SAMHD1 A565T ox-mtDNA→cGAS-STING/NLRP3 loops even though SAMHD1 itself is not mentioned.
DOI: 10.3389/fimmu.2026.1921226

Leptin attenuates heat stress-induced mitoxyperilysis in porcine Sertoli cells by suppressing the mtDNA-cGAS-STING axis. (from veterinary reproductive biology/animal science)
Guo Ming; Zhang Jinyang; Gu Shanshan; Gao Yawen; Zhu Zhendong — Journal of animal science and biotechnology 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NF-kB-IKK, mito-ROS-NF-kB, treatment-target

Demonstrates VDAC1-mediated mtDNA leakage activating cGAS-STING-TBK1-IRF3/NF-κB axis and inflammatory cytokine production, directly paralleling the BLUE pathway mechanism in the SAMHD1 model, with leptin as a novel mitochondrial-protective therapeutic modulator of this axis.
DOI: 10.1186/s40104-026-01489-6

Gut microbiota–mitochondria–barrier–multiorgan axis: a network-based hypothesis for systemic injury (from Gastroenterology/Critical Care Medicine)
Yachao Li; Huai-Jue Qiu; Xiang Gao; Yanling Zhang; Qin Xia — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, clinical-phenotype

Describes mtDNA/mtDAMP-driven cGAS-STING and NLRP3 activation as a mechanistic hub linking mitochondrial dysfunction to systemic inflammation, paralleling the SAMHD1-driven Loop A/B mitochondrial-innate immune convergence though in a gut-microbiota context rather than SAMHD1 pathway directly.
DOI: 10.3389/fimmu.2026.1885379

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Quantitative adaptor heterogeneity sets single-cell thresholds for innate immune activation and attenuation (from single-cell biophysics/systems immunology)
Dey Arpan; Cui Yuhao; Nawalpuri Bharti; Meisl Georg; Sewell Gavin — preprint (preprint) 2026
Score: 4/10 | Pathways: NF-kB-IKK, other

This paper studies MyD88/TLR-driven NF-κB signaling heterogeneity in macrophages, tangential to the SAMHD1-cGAS-STING-NLRP3-NF-κB interferonopathy axis but not directly connected to SAMHD1, dNTP metabolism, or mitochondrial pathology.
DOI: 10.21203/rs.3.rs-10682444/v1

Mutant p53 Gain-of-Function and Immune Suppression: Mathematical Modeling of STING-TBK1-IRF3 Axis Restoration for Enhanced Cancer Therapy. (from computational oncology/mathematical biology)
Omer Salaheldin; Ouifki Rachid; Mambili-Mamboundou Hermane — Mathematical biosciences 2026
Score: 4/10 | Pathways: cGAS-STING

This is a mathematical modeling paper about mutant p53 suppression of the STING-TBK1-IRF3 axis in cancer immune evasion, touching the same IFN-I signaling node relevant to SAMHD1 biology but with no connection to SAMHD1, dNTP metabolism, or the family phenotype.
DOI: 10.1016/j.mbs.2026.109806

NLRP3 Inflammasome Activation and Atherogenic Lipid Profile in Hemodialysis Patients. (from Nephrology/dialysis)
Abdelaziz Mohammed N; Elshabrawy Nehal; Almenshawy Ahmed; Elsodany Karim A; Elka — Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 2026
Score: 3/10 | Pathways: NLRP3

Studies NLRP3 inflammasome and lipid atherogenicity in hemodialysis patients without any SAMHD1, interferon, or mitochondrial dNTP connection, only tangentially touching the NLRP3 node in this framework.
DOI: 10.1002/1744-9987.70158

Precision genome editing strategies for enduring lipid lowering in atherosclerosis. (from Cardiology/lipidology gene therapy)
Chowdhury Durlav; Singh Nirdesh; Garai Swarnalata; Pandey Devi Prasad; Bodakhe S — European journal of pharmacology 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews precision genome editing (CRISPR, base/prime editing, AAV/LNP delivery) for lipid-lowering in atherosclerosis, offering only generic technology overlap with gene therapy correction strategies but no SAMHD1, interferonopathy, or mitochondrial pathway relevance.
DOI: 10.1016/j.ejphar.2026.179312

NIR-II Small-Molecule Shuttle-Like Nanoassemblies for Mild-Temperature NIR-II Photothermal Enhanced Cuproptosis/STING Activation and Cancer Immunotherapy. (from oncology nanomedicine/photothermal therapy)
Dong Xue; Zhu Junfan; Sun Ying; Li Nianshu; Dai Shipeng — 2026
Score: 3/10 | Pathways: cGAS-STING, VDAC1

This is a cancer nanomedicine paper using mtDNA-release/cGAS-STING activation as an immunotherapy mechanism in tumors, unrelated to SAMHD1 haploinsufficiency but tangentially touching the same downstream cGAS-STING/mtDNA-release pathway.
DOI: 10.1002/smll.75620

Pathway Coverage This Week

  • cGAS-STING: 7 papers
  • NLRP3: 5 papers
  • treatment-target: 5 papers
  • clinical-phenotype: 4 papers
  • mito-ROS-NF-kB: 4 papers
  • VDAC1: 3 papers
  • JAK-STAT: 2 papers
  • NF-kB-IKK: 2 papers
  • AGS-spectrum: 1 papers
  • POLG-mtDNA: 1 papers
  • ME-CFS: 1 papers
  • mTOR-lysosomal: 1 papers
  • urate-NLRP3: 1 papers
  • other: 1 papers
  • prime-editing: 1 papers
  • gene-therapy-delivery: 1 papers

SAMHD1 Research Digest — 2026-08-30

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 22 papers evaluated | 3 high-relevance (≥7) | 7 medium (5–6) | 12 low (3–4) | 0 scored <3

⚠️ Partial run: preprint returned no papers (likely rate-limited). Coverage this week is incomplete; the missed papers are not marked seen and will be picked up on the next run.

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Iterative genetic testing identifies SAMHD1 deficiency caused by a homozygous balanced translocation. (from Clinical genetics/genomics (structural variant diagnostics))
Baker Paul J; Zhang Yaoyuan; Bishop Imogen; Cleveland Madeline L; McAllan Alexan — Journal of human immunity 2026
Score: 9/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, dNTPase, clinical-phenotype

Directly demonstrates SAMHD1 loss-of-function via a novel structural variant (balanced translocation) causing type I interferon signature and familial chilblain lupus, reinforcing the core SAMHD1-interferonopathy mechanism relevant to the A565T haploinsufficiency model.
DOI: 10.70962/jhi.20260044

Mitophagy mitigates mitochondrial DNA-induced activation of cGAS-STING in autoimmune thyroiditis (from Endocrinology (autoimmune thyroiditis))
Xiao-Chen Xie; Yang Guo; Ran Guo; Yongze Li; Shan-Shan Wang — Nature Communications 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, NF-kB-IKK, treatment-target, clinical-phenotype

Demonstrates that mitophagy failure (PINK1/Parkin/TAX1BP1 axis, mechanistically parallel to ISG15-mediated mitophagy block in the RED stream) causes mtDNA leakage and cGAS-STING-driven autoimmune inflammation, directly reinforcing the BLUE/RED loop mechanism and validating STING inhibition (C176) as a therapeutic strategy relevant to the SAMHD1 interferonopathy model.
DOI: 10.1038/s41467-026-76047-9

APOE4-AGE axis is linked to mtDNA release and cGAS-STING mediated neuroinflammation in the aging brain. (from Neurodegeneration/Alzheimer's disease research)
Akhter Firoz; Akhter Asma; Zhou Jasmine; Xi Michelle; Zhu Donghui — Free radical biology & medicine 2026
Score: 7/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, clinical-phenotype

Demonstrates mtDNA release triggering cGAS-STING-TBK1-IRF3-driven type I interferon and neuroinflammation via mitochondrial dysfunction, directly paralleling the BLUE loop mechanism (VDAC1/mtDNA/cGAS/STING/IFN-I) central to the SAMHD1 syndrome, though in an APOE4/AGE-RAGE rather than SAMHD1 context.
DOI: 10.1016/j.freeradbiomed.2026.08.054

🟡 Medium Relevance (Score 5–6)

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

Mitochondrial immunometabolism in sepsis: bridging immune cell dysfunction and organ failure (from Critical care/sepsis immunometabolism)
Xingzhan Zhang; Ling Zhao; Wei Fu; Lili Pan; Huanhuan Wu — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

Reviews mitochondrial mtDNA/mtROS-driven cGAS-STING and NLRP3 activation and its crosstalk with NF-kB in immune cells, mechanistically overlapping with the BLUE/PURPLE/GOLD loops in the SAMHD1 model even though sepsis rather than SAMHD1 haploinsufficiency is the trigger.
DOI: 10.3389/fimmu.2026.1921226

Interferon Regulatory Factors as Potential Therapeutic Targets in Cardiovascular Disease: Focusing on Vascular Inflammation (from Cardiology/vascular biology)
Chen-Xi Bai; Wei-Xu Liu; Yu-Bo Wang; Hui-Xia Zhu; Xing Fan — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, NF-kB-IKK, treatment-target

Reviews IRF1/3/5/7 pro-inflammatory signaling via cGAS-STING/NLRP3/NF-kB/JAK-STAT in vascular disease, mechanistically parallel to the IFN-I/NLRP3 axis in SAMHD1 A565T interferonopathy but without direct SAMHD1 or mitochondrial dNTP linkage, and offers cardiovascular relevance given the family's cardiac/vascular phenotype risk.
DOI: 10.3390/ijms27177647

p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages. (from virology/pharmacology (HIV restriction and nutraceutical NRF2 signaling))
Marcelino Bianka Nicolle Pena; Girard Kiersten; Letourneau Lauren; Lewin Andrew; — Biomolecules 2026
Score: 6/10 | Pathways: dNTPase, treatment-target, other

Demonstrates regulation of SAMHD1 phosphorylation (T592) via p21/CDK in macrophages and its role in antiviral restriction, relevant to SAMHD1 functional regulation though not the A565T dNTPase catalytic mechanism directly.
DOI: 10.3390/biom16081213

Investigating the Role of Type I Interferon Signaling on Muscle Disease Using Mouse Models. (from Rheumatology/Muscle disease (myositis))
Spathis Rita; Narvesen Sabrina; Robles Kuriplach Deeva; Huang Karen; Sundar Teja — Arthritis & rheumatology (Hoboken, N.J.) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates JAK inhibitor (tofacitinib) suppression of type I IFN signature and improved survival in murine myositis models driven by IFN-beta overexpression, directly supporting JAK-STAT as a therapeutic target relevant to the SAMHD1 interferonopathy mechanism though not SAMHD1-specific.
DOI: 10.1002/art.70096

Development of mitochondrial mutator pigs exhibiting increased mitochondrial DNA mutations and premature aging via prime editing. (from Comparative/translational aging biology using large-animal (porcine) prime-editing models)
Chen Fangbing; Liang Yanhui; Zheng Wei; Yao Aobo; Wang Ning — Science advances 2026
Score: 5/10 | Pathways: POLG-mtDNA, prime-editing, gene-therapy-delivery

Demonstrates POLG proofreading-deficiency-driven mtDNA mutation accumulation and premature aging using prime editing in a large animal model, directly relevant to the PURPLE-stream POLG stalling node and to prime-editing technology tracked for future SAMHD1 correction, though not immune-cell or SAMHD1-specific.
DOI: 10.1126/sciadv.adu0632

Alcohol intake reprograms hepatic immune-metabolic circuits to exacerbate murine atherosclerosis and human cardiovascular risk. (from Hepatology/Cardiology)
Hoebinger Constanze; Semmler Georg; Petrenko Oleksandr; Rajcic Dragana; Hoffelne — JHEP reports : innovation in hepatology 2026
Score: 5/10 | Pathways: urate-NLRP3, NLRP3, clinical-phenotype

Demonstrates hyperuricemia-driven hepatic NLRP3 upregulation and inflammasome activation linked to dyslipidemia and cardiovascular risk, paralleling the GOLD pathway (dGTP→purine catabolism→uric acid→NLRP3) in the SAMHD1 model though not SAMHD1-specific.
DOI: 10.1016/j.jhepr.2026.101932

Understanding cardiovascular aging as a disorder of mitochondrial network (from Cardiology/cardiovascular aging)
Taslima Akter Shila; Dhrubo Ahmad; Jianli Zhao; Huilan Tan; Bo Wang — The journal of cardiovascular aging 2026
Score: 5/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, clinical-phenotype

This review discusses mitochondrial DNA/vesicle release activating cGAS-STING and driving sterile inflammation in cardiovascular aging, which parallels the SAMHD1-driven mitochondrial-interferon mechanism but lacks direct SAMHD1 or NLRP3/inflammasome linkage and focuses on aging rather than the specific disease pathway.
DOI: 10.20517/jca.2026.07

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

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

Discusses cGAS-STING and NLRP3 mitochondrial danger-signal pathways shared with the SAMHD1 mechanism but in an osteoarthritis mechanical-loading context unrelated to SAMHD1 dysfunction or the family phenotype spectrum.
DOI: 10.3389/fimmu.2026.1931112

Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts (from Mitochondrial biochemistry/virology (PTM signaling biology))
Nao Morimoto; Tomohiko Okazaki — Frontiers in Physiology 2026
Score: 4/10 | Pathways: cGAS-STING, VDAC1, other

This paper details PTM regulation of MAVS, a mitochondrial RLR adaptor producing type I IFN, offering a conceptually parallel but mechanistically distinct pathway to the SAMHD1-VDAC1-cGAS-STING axis without direct SAMHD1 or NLRP3/ISG15 involvement.
DOI: 10.3389/fphys.2026.1907325

Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design. (from genome engineering/synthetic biology)
Muhammad Waqar; Cao Xi; Umar Aziz; Nauman Khan; Jiao Ziao — Biodesign research 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing technology advances with no immune/myeloid-specific application or SAMHD1 correction focus, offering only background relevance to future gene therapy translation.
DOI: 10.1016/j.bidere.2026.100104

The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling. (from exercise physiology/skeletal muscle biology)
Sangha Jada; Hood David A — Biomolecules 2026
Score: 4/10 | Pathways: NLRP3, mito-ROS-NF-kB

Reviews mitochondrial DAMP-driven NLRP3 activation and exercise mitigation in skeletal muscle, relevant to the mitochondrial-inflammasome mechanism but lacks SAMHD1, interferon, or clinical-phenotype connections central to this disease profile.
DOI: 10.3390/biom16081218

Glyphosate induces intestinal inflammatory injury associated with mitochondrial-lysosomal dysfunction, cGAS-STING activation, and pyroptosis-related responses in common carp (Cyprinus carpio L.). (from aquatic toxicology/veterinary environmental science)
Zhang Shuyue; Ji Xiaofeng; Zhong Haoyu; Wang Zehui; Li Xiaohui — Fish & shellfish immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB

This fish toxicology study demonstrates mtDNA release-cGAS-STING-NLRP3-pyroptosis signaling analogous to Loop A/B mechanisms in the SAMHD1 model, but is a non-mammalian xenobiotic toxicity paper without direct genetic or clinical relevance to SAMHD1 haploinsufficiency.
DOI: 10.1016/j.fsi.2026.111682

Non-invasive Ultra-early in Utero Detection and Precision CRISPR-mediated Correction of Monogenic Embryonic Mutations: A Critical Appraisal of a Hypothetical Therapeutic Framework (from Prenatal diagnostics / gene therapy delivery)
S. Bittmann; E. Luchter; E. Moschüring-Alieva — Asian Journal of Medicine and Health 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery, pregnancy-fetal

This is a general critical review of in utero cfDNA detection and CRISPR/prime-editing correction for monogenic disease, not specific to SAMHD1 or its core inflammatory pathways, but tangentially relevant as background for future gene-correction strategies applicable to a heterozygous missense variant like A565T.
DOI: 10.9734/ajmah/2026/v24i91427

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

This is a general nephrology review of immune-mediated kidney diseases touching on shared innate-immune pathways (NLRP3, cGAS-STING, NF-kB, JAK-STAT) that overlap thematically with the SAMHD1 interferon-mitochondrial mechanism but has no direct SAMHD1, mitochondrial dNTP, or ME/CFS/family phenotype connection.
DOI: 10.3389/fcell.2026.1878787

A PepFect14 analog improves non-viral CRISPR delivery in primary human cells to facilitate genome editing and repair. (from Dermatology/gene therapy bioengineering)
A. du Rand; Courtney Masterson; Daniel J Verdon; Andrew Siow; E. Loef — Bioengineering & translational medicine 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes a non-viral CRISPR delivery peptide for skin cell genome editing in epidermolysis bullosa, which is a gene-editing delivery advance but not targeted at myeloid/immune cells or SAMHD1 correction and thus only tangentially related.
DOI: 10.1002/btm2.70172

Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system (from pulmonology/pharmaceutics)
Fangru Jia; Linlin Ma; Yanan Li — International Journal of Pharmaceutics: X 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This review covers mRNA-LNP delivery to lung tissue generally, with only tangential relevance to SAMHD1 gene therapy since it doesn't address myeloid/HSC editing or immune cell delivery specific to the disease model.
DOI: 10.1016/j.ijpx.2026.100634

Neurotensin receptor agonist PD149163 modulates LPS-induced sub-acute gut inflammation by inhibiting TLR4/NF-κB/NLRP3 inflammasome pathway: In vivo, in silico and network pharmacology analyses. (from Gastroenterology/pharmacology)
Singh Priya; Mohanty Banalata — International immunopharmacology 2026
Score: 3/10 | Pathways: NLRP3, NF-kB-IKK

This paper studies TLR4/NF-κB/NLRP3 inhibition by a neurotensin receptor agonist in LPS-induced gut inflammation in mice, sharing pathway components with the SAMHD1 model but with no connection to SAMHD1, interferonopathy, or mitochondrial dNTP mechanisms.
DOI: 10.1016/j.intimp.2026.117321

Pain and Analgesic Doses Versus Free Interleukin 18 (IL-18F) Blood Levels Following Surgery: A Prospective Randomized Study of Patients With Minilaparotomy Cholecystectomy Versus Laparoscopic Cholecystectomy. (from Surgery/pain medicine)
Eskelinen Matti; Kuosmanen Viivi; Selander Tuomas; Kaarniranta Kai; Saimanen Iin — In vivo (Athens, Greece) 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype

This paper studies IL-18/IL-18BP as postoperative pain biomarkers after cholecystectomy, touching the NLRP3-IL-18 axis and the family's cholecystectomy clustering phenotype but without any SAMHD1, interferon, or mitochondrial mechanism linkage.
DOI: 10.21873/invivo.14435

Generation of two homozygous iPSC lines carrying variants of uncertain significance in LMNA associated with cardiomyopathy. (from Cardiology/stem cell genetics)
Liu Lu; Wu David; Manhas Amit; Noishiki Chikage; Tripathi Dipti — Stem cell research 2026
Score: 3/10 | Pathways: prime-editing

This paper demonstrates prime editing to generate LMNA VUS iPSC lines for cardiomyopathy research, technically relevant to gene correction methodology but unrelated to SAMHD1 or its associated pathways.
DOI: 10.1016/j.scr.2026.104086

Pathway Coverage This Week

  • cGAS-STING: 10 papers
  • NLRP3: 9 papers
  • clinical-phenotype: 7 papers
  • mito-ROS-NF-kB: 6 papers
  • treatment-target: 5 papers
  • gene-therapy-delivery: 5 papers
  • JAK-STAT: 4 papers
  • NF-kB-IKK: 4 papers
  • prime-editing: 4 papers
  • dNTPase: 2 papers
  • other: 2 papers
  • AGS-spectrum: 1 papers
  • ISG15-mitophagy: 1 papers
  • POLG-mtDNA: 1 papers
  • urate-NLRP3: 1 papers
  • VDAC1: 1 papers
  • pregnancy-fetal: 1 papers

SAMHD1 Research Digest — 2026-08-23

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 16 papers evaluated | 1 high-relevance (≥7) | 6 medium (5–6) | 9 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Targeting mPTP with NIM811 Alleviates Pancreatic Injury and Inflammatory Response in Severe Acute Pancreatitis (from Gastroenterology/Critical Care (acute pancreatitis))
Feng Dan; Zhang Jia-Rui; Bai Xue; Chen Xia — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target, other

Demonstrates mPTP/VDAC-adjacent mitochondrial membrane permeability leading to mtDNA release and cGAS-STING-driven inflammatory cytokine production (IL-1β, IL-6, TNF-α) in a mitochondrial damage model, directly paralleling the BLUE loop mechanism (mtDNA escape → cGAS/STING → IFN-inflammatory output) though in a distinct disease context (pancreatitis) without SAMHD1 involvement.
DOI: 10.21203/rs.3.rs-10616969/v1

🟡 Medium Relevance (Score 5–6)

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

The dual role of the cGAS-STING signaling pathway in kidney diseases: from acute injury to chronic fibrosis – molecular mechanisms and precision therapeutic strategies (from Nephrology)
Guangdong Qi; Fei Xue; Hualin Sun; Xinlei Yao; Qingyuan Liu — Frontiers in Pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Reviews cGAS-STING mechanisms (mtDNA leakage, TBK1-IRF3/NF-kB, inflammation-fibrosis) and inhibitor strategies directly relevant to the BLUE loop pathway, though applied to renal disease rather than SAMHD1 context.
DOI: 10.3389/fphar.2026.1882994

Quercetin induces molecular hallmarks of immunogenic cell death and cGAS-STING pathway activation via mitochondrial DNA release in hepatocellular carcinoma cells. (from Oncology/pharmacology)
Lin Tong; Chen Yifan; Huang Zhengrong — Naunyn-Schmiedeberg's archives of pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates mtDNA release triggering cGAS-STING-TBK1-IRF3/p65 activation, directly modeling the core Loop A/NF-kB crosstalk mechanism though in an oncology drug-induction context rather than SAMHD1 dysfunction.
DOI: 10.1007/s00210-026-05815-7

Expanding the therapeutic landscape of Still's disease: the emerging role of JAK inhibitors. (from Rheumatology)
Ruscitti Piero; Ursini Francesco; Giacomelli Roberto; Cantarini Luca; Caso Franc — Expert opinion on pharmacotherapy 2026
Score: 6/10 | Pathways: JAK-STAT, NLRP3, treatment-target, clinical-phenotype

Reviews JAK inhibitors modulating IL-1/IL-6/IFN-γ and inflammasome-dependent pathways in Still's disease, directly relevant to the JAK-STAT and NLRP3 nodes and to JAKi therapeutic strategies applicable to the interferon-mitochondrial syndrome, though not SAMHD1-specific.
DOI: 10.1080/14656566.2026.2723582

Mitochondrial DNA in necrosis-like cell death in failing hearts: evidence and mechanisms fostering damage. (from cardiology)
Marciníková Andrea; Jarabicová Izabela; Horváth Csaba; Adameova Adriana — American journal of physiology. Cell physiology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, other

This cardiology-focused review details mtDNA release triggering cGAS-STING and NLRP3/AIM2 inflammasome pathways driving necroptosis/pyroptosis in heart failure, mechanistically overlapping with the BLUE loop (VDAC1/mtDNA/cGAS-STING) and NLRP3 activation streams central to the SAMHD1 disease model, though it does not address SAMHD1 or dNTPase biology directly.
DOI: 10.1152/ajpcell.00266.2026

The Role of Skeletal Muscle Mitochondria in NRLRP3 Inflammasome Signaling (from exercise physiology/skeletal muscle biology)
Jada Sangha; David A. Hood — Biomolecules 2026
Score: 5/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Reviews NLRP3 inflammasome activation via mitochondrial DAMPs (ROS, oxidized mtDNA) in skeletal muscle, mechanistically overlapping with the disease's mitochondrial-inflammasome axis but without SAMHD1, cGAS-STING, or IFN-I context, and exercise/myokine focus is only indirectly relevant to ME/CFS fatigue phenotype.
DOI: 10.3390/biom16081218

Systemic effects of gout flares beyond the joints. (from Rheumatology/Cardiology)
Cipolletta Edoardo; Mamas Mamas A; Abhishek Abhishek — Current opinion in rheumatology 2026
Score: 5/10 | Pathways: urate-NLRP3, NLRP3, treatment-target

Discusses gout flare-driven NLRP3/IL-1β activation and cardiovascular sequelae, directly relevant to the GOLD stream (dGTP→uric acid→MSU crystals→NLRP3) and family gout/uric acid phenotype but not tied to SAMHD1 or interferon mechanisms.
DOI: 10.1097/BOR.0000000000001183

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Atomic-Level Strain-Engineered Piezoelectric Nanosheets for cGAS-STING Activation. (from materials science/nanomedicine oncology)
Yang Lu; Zang Pengyu; Zhang Rui; Yang Meiqi; Yu Chenghao — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target

This paper describes a nanomaterial-based tumor immunotherapy that activates cGAS-STING via mtDNA release, sharing a mechanistic node with the disease's BLUE pathway but in an unrelated oncologic engineering context with no SAMHD1 or interferonopathy relevance.
DOI: 10.1002/anie.5643285

Mitochondrial metabolic remodelling during bacterial infection: Molecular mechanisms, cellular consequences, and therapeutic opportunities. (from Microbiology/Infectious Disease)
Kowalik Agnieszka; Paszenda Patrycja; Frątczak Agnieszka; Piwowar Adrian; Obryck — Tissue & cell 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB

This review covers mitochondrial-immune crosstalk mechanisms (cGAS-STING, NLRP3, ROS-NF-kB, mitochondrial fragmentation) overlapping with the disease's core pathways, but is focused on bacterial infection biology rather than SAMHD1 dysfunction or interferonopathy syndromes.
DOI: 10.1016/j.tice.2026.103873

Gut microbiota–mitochondria–barrier–multiorgan axis: a network-based hypothesis for systemic injury (from Gastroenterology/critical care medicine)
Yachao Li; Huaijue Qiu; Xia Gao; Yanling Zhang; Qin Xia — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, other

This paper discusses cGAS-STING and NLRP3 activation via mitochondrial DAMPs in a gut-microbiota-critical illness context, sharing core mechanistic pathways but lacking any SAMHD1, interferonopathy, or family phenotype connection.
DOI: 10.3389/fimmu.2026.1885379

Genome Editing in Primary Mammalian Cells via Electroporation of Editor RNA. (from molecular biology/gene editing methodology)
Maria Viskadourou; J. Workman; Emma V Burke; D. M. Eckley; Johannes Dohr — Journal of visualized experiments : JoVE 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General methods paper on mRNA-based genome editing delivery in primary cells, relevant as generic platform technology for future SAMHD1 correction but not disease-specific or immune/myeloid-focused.
DOI: 10.3791/71449

FGFR4 suppresses antitumor immunity and cuproptosis by disrupting CYLD-mediated stabilization of STING and FDX1. (from Oncology (tumor immunology/cancer therapeutics))
Zhong Hongguang; Huang Ruixuan; Deng Wenyuan; Ruan Ruiwen; Dai Xiaofeng — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target, other

This paper involves cGAS-STING pathway regulation via CYLD/FDX1/cuproptosis in cancer immunotherapy, but is oncology-focused with no connection to SAMHD1, dNTP metabolism, or interferonopathy mechanisms central to this disease profile.
DOI: 10.1016/j.canlet.2026.218790

Epithelial interferon-stimulated gene programs modulate chemotherapy sensitivity in colorectal cancer via EPSTI1. (from Oncology)
Erkan Erdogan Pekcan; Hämäläinen Emmi; Kolikova Julia; Nikupaavola Tiia; Sajnani — Oncogene 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Discusses JAK-STAT/ISG program and ruxolitinib in a colorectal cancer oncology context, tangentially touching interferon signaling but without SAMHD1, mitochondrial, or innate immune inflammasome mechanisms central to the disease profile.
DOI: 10.1038/s41388-026-03957-9

Dysfunction of the Neurovascular Unit in Diabetic Retinopathy: Advances from Molecular Mechanisms to Targeted Interventions. (from Ophthalmology)
Zhao Chunning; Qin Leilei; Zhang Jing; Wang Xiu — Stem cell reviews and reports 2026
Score: 3/10 | Pathways: NLRP3, other

This is a diabetic retinopathy review touching on NLRP3/mitochondrial dysfunction in a generic ophthalmology context, without any SAMHD1, interferon, or family-phenotype linkage.
DOI: 10.1007/s12015-026-11213-6

Alopecia Areata: Current and Emerging Therapies. (from Dermatology)
Domingues João; King Brett; Torres Tiago — Drugs 2026
Score: 3/10 | Pathways: JAK-STAT, treatment-target

Reviews JAK inhibitors (baricitinib) for alopecia areata, relevant as a JAK-STAT therapeutic class overlapping with interferonopathy management but not directly tied to SAMHD1 mechanism or family phenotypes.
DOI: 10.1007/s40265-026-02371-5

Integrated Multi-omics Reveals CDKN1A Suppression and Metabolic Regulation as Key Mechanisms of Huangqi Guizhi Wuwu Decoction Against Doxorubicin-Induced Cardiotoxicity. (from Cardio-oncology/pharmacology (traditional Chinese medicine))
Hou Qian; Yu Xinyue; Wu Ke; Chen Siling; Mao Xin — Cardiovascular toxicology 2026
Score: 3/10 | Pathways: ISG15-mitophagy, other

This paper on a Chinese herbal decoction mitigating doxorubicin cardiotoxicity incidentally identifies Irf7/Isg15 and apoptosis genes (Bax, Cdkn1a) but has no mechanistic connection to SAMHD1, interferonopathy, or the core inflammasome/mitochondrial pathways central to this disease profile.
DOI: 10.1007/s12012-026-10168-x

Pathway Coverage This Week

  • treatment-target: 11 papers
  • cGAS-STING: 8 papers
  • NLRP3: 7 papers
  • other: 6 papers
  • NF-kB-IKK: 3 papers
  • JAK-STAT: 3 papers
  • mito-ROS-NF-kB: 3 papers
  • VDAC1: 1 papers
  • clinical-phenotype: 1 papers
  • urate-NLRP3: 1 papers
  • prime-editing: 1 papers
  • gene-therapy-delivery: 1 papers
  • ISG15-mitophagy: 1 papers

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 — 2026-08-09

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 21 papers evaluated | 2 high-relevance (≥7) | 9 medium (5–6) | 10 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Senkyunolide I Inhibits mtDNA-cGAS-STING Signaling in Macrophages via Targeting VDAC1 Oligomerization to Attenuate Ulcerative Colitis. (from Gastroenterology (ulcerative colitis/IBD))
Ye Zhiming; Huang Yihang; Han Bohao; Zhang Lei; Yu Can — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, NLRP3, treatment-target

Directly demonstrates VDAC1 oligomerization-mediated mtDNA release driving cGAS-STING-NLRP3 activation in macrophages, mechanistically identical to the BLUE loop, with a novel small-molecule inhibitor (SEI) analogous to VBIT-4 as a therapeutic strategy.
DOI: 10.1002/advs.77045

Yiqi Huoxue Jiedu formula protects against sepsis-associated lung injury by modulating macrophage mitophagy and mtDNA-STING signaling. (from Traditional Chinese Medicine / critical care sepsis pulmonology)
Ma Shuqi; Pan Qiusha; Lin Jingnan; Zeng Ruifeng; Xi Xiaotu — Chinese medicine 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target, mito-ROS-NF-kB

Demonstrates a PINK1/Parkin mitophagy–mtDNA leakage–cGAS-STING-TBK1-IRF3-IFN-I axis in macrophages, directly paralleling the BLUE/RED loops and mitophagy blockade mechanisms central to the SAMHD1 syndrome model, with a botanical treatment implication for mitophagy restoration.
DOI: 10.1186/s13020-026-01475-0

🟡 Medium Relevance (Score 5–6)

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

The dual role of the cGAS-STING signaling pathway in kidney diseases: from acute injury to chronic fibrosis – molecular mechanisms and precision therapeutic strategies (from Nephrology)
Guangdong Qi; Fei Xue; Hualin Sun; Xinlei Yao; Qingyuan Liu — Frontiers in Pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, NF-kB-IKK

Reviews cGAS-STING mechanisms (mtDNA leakage, TBK1-IRF3/NF-κB, PERK-eIF2α) and inhibitor strategies (H-151, RU.521) directly relevant to the BLUE loop's core signaling axis, though applied to renal rather than SAMHD1-driven disease.
DOI: 10.3389/fphar.2026.1882994

Maternal hyperglycemia-induced O-GlcNAcylation of CaMKIIδ promotes mtDNA release and cardiac remodeling in offspring. (from Cardiology/Obstetrics (maternal-fetal medicine and pediatric cardiology))
Xiao Zemeng; Gao Ling; Wang Yuehong; Yang Chunli; Qian Yuxuan — 2026
Score: 6/10 | Pathways: cGAS-STING, pregnancy-fetal, NF-kB-IKK, clinical-phenotype

This paper demonstrates a mtDNA-release → cGAS-STING → inflammation axis in cardiac tissue analogous to the BLUE loop mechanism in the SAMHD1 profile, with pregnancy/fetal programming relevance to the family's obstetric phenotype tracking.
DOI: 10.1038/s41467-026-75630-4

Unraveling Immune Dysregulation in ZNFX1 Deficiency: From Interferonopathies to Macrophage Activation Syndrome (from Clinical immunology/rare monogenic autoinflammatory disease)
Sara G. Hamad; Melanie Makhlouf; N. Agrebi; A. Kaddourah; M. Abu-Hasan — Journal of Clinical Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, IRF7-metabolic, AGS-spectrum, clinical-phenotype, treatment-target

ZNFX1 deficiency is a related type I interferonopathy involving MAVS/ISG dysregulation with NF-kB/NLRP3-adjacent inflammatory cytokine (TNF, IL-1beta) crosstalk and macrophage activation syndrome, offering mechanistic and clinical analogy to the SAMHD1 interferon-mitochondrial syndrome despite a distinct causal gene.
DOI: 10.1007/s10875-026-02056-4

Hyper-aging in systemic sclerosis: linking genome instability, mitochondrial dysfunction, and inflammaging to fibrosis. (from Rheumatology (systemic sclerosis/aging biology))
Mohammad Waseem; Azait Imtiaz; Amit Datta; Rafael Contreras-Galindo — Current opinion in rheumatology 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, treatment-target, clinical-phenotype

Describes cytosolic DNA (nuclear/mitochondrial)-driven cGAS-STING/type I IFN activation, mitochondrial dysfunction, and genome instability driving fibrosis in systemic sclerosis, mechanistically paralleling the BLUE/RED interferonopathy streams and suggesting rheumatologic phenotype overlap relevant to the family's autoimmune/mitochondrial spectrum.
DOI: 10.1097/BOR.0000000000001181

AI Designed Conformation Locking Peptides Target STING to Restore Diabetic Wound Healing. (from dermatology/wound healing and biomaterials engineering)
Li Xinyu; Fu Haojie; Wang Zhe; Chen Xuanzhou; Zhang Ruhong — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

This paper targets the STING-TBK1-IRF3 axis directly implicated in the disease's BLUE loop, offering a novel therapeutic conformation-locking peptide strategy relevant to interferonopathy suppression, though applied to diabetic wound healing rather than SAMHD1-related pathology.
DOI: 10.1002/advs.76849

DNA Sensing Pathways in Innate Immunity: Implications for Alzheimer’s Disease Progression and Therapy (from neurology/neurodegeneration)
Chenmo Shi; Ye Liu; Yanli Zhu — Molecular Neurobiology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Reviews cGAS-STING/AIM2/TLR9 DNA-sensing driving IFN-I and inflammasome-mediated neuroinflammation, directly relevant to the interferon-mitochondrial mechanism though applied to Alzheimer's rather than SAMHD1 disease, offering a neurology/neuroinflammation bridge to the family's neurologic phenotypes.
DOI: 10.1007/s12035-026-06081-7

The consequences of mitochondrial dysfunction and upregulated glycolysis on innate and adaptive immune responses (from Metabolic immunology / cancer immunometabolism)
Fabrizio Marcucci; Cristiano Rumio — Cell Signaling, Inflammation & Disease 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, POLG-mtDNA, other

Reviews oxidized mtDNA/ROS-driven innate immune activation and glycolytic immunomodulation converging on mitochondrial dysfunction, mechanistically adjacent to the NLRP3/mito-ROS-NF-kB streams in the SAMHD1 model but without cGAS-STING/NLRP3-specific inflammasome or SAMHD1 data.
DOI: 10.1186/s44505-026-00005-x

Impaired NADH-linked mitochondrial respiration disrupts ventral midbrain neuronal programs in POLG disease. (from Neurology/mitochondrial disease (stem cell organoid modeling))
Chen Anbin; Yangzom Tsering; Sullivan Gareth John; Liang Kristina Xiao — Journal of translational medicine 2026
Score: 6/10 | Pathways: POLG-mtDNA, treatment-target

This paper studies POLG mutations causing mitochondrial DNA instability and impaired oxidative phosphorylation in dopaminergic neurons, directly relevant to the PURPLE stream's POLG stalling mechanism even though it lacks any immune/inflammasome readout.
DOI: 10.1186/s12967-026-08706-w

Early versus late JAK-STAT-IFN signaling distinguishes no rejection from subclinical to clinical TCMR after liver transplantation. (from Transplant hepatology/immunology)
Macedo Camila; Hadjiyannis Yannis; Tran Lillian M; Elinoff Beth D; Abukhiran Ibr — Science translational medicine 2026
Score: 5/10 | Pathways: JAK-STAT, treatment-target

Demonstrates biphasic JAK-STAT/interferon-stimulated gene signaling driving T cell-mediated rejection and validates ruxolitinib (a JAK inhibitor relevant to the disease's IFN-I axis) as a therapeutic strategy, though not SAMHD1-specific.
DOI: 10.1126/scitranslmed.aec4107

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

SAMHD1 enhances HIV-1-induced glycolysis in monocytic cells through hexokinase 2 upregulation (from Virology/HIV metabolism)
Yang Hua; Cheung Pak-Hin Hinson; Wu Li — 2026
Score: 4/10 | Pathways: dNTPase, mito-ROS-NF-kB, other

This paper explores a novel SAMHD1 function in HIV-1-induced glycolysis and mitochondrial ROS in monocytic cells, which is tangential to the interferon-mitochondrial-NLRP3 axis central to the A565T phenotype but still reinforces SAMHD1's broader mitochondrial regulatory role.
DOI: 10.64898/2026.08.03.742570

Precision correction of the GJB2 c.235delC mutation by prime editing in vitro. (from Otology/audiology gene therapy)
Jin Jiang; Lv Xiujuan; Li Yangyang; Xu Yaoyao; Chen Lei — Gene therapy 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates a generalizable prime editing/dual-AAV correction toolkit for a monogenic point mutation, methodologically relevant to future SAMHD1 missense correction but unrelated to GJB2's disease mechanism or the interferon-mitochondrial pathways.
DOI: 10.1038/s41434-026-00638-w

AI-driven LNP design: unlocking non-viral delivery for cell and gene therapy (from Pharmaceutics/Drug Delivery Engineering)
Bowen Li — Cell and Gene Therapy Insights 2026
Score: 4/10 | Pathways: gene-therapy-delivery

Discusses general AI-guided LNP design for non-viral gene therapy delivery, relevant as a future therapeutic platform but not specific to SAMHD1, myeloid/immune tissue targeting, or interferon-mitochondrial mechanisms.
DOI: 10.18609/cgti.2026.082

Co-delivery of lentiviral vectors and Cas9-containing virus-like particles enables rapid, scalable manufacture of gene-edited CAR T cells. (from Cell and gene therapy manufacturing / oncology immunotherapy)
Ferrara Francesca; Wielgosz Matthew M; Park Jeoungeun J; Bauler Matthew; Wincek * — Molecular therapy. Advances 2026
Score: 4/10* | Pathways: gene-therapy-delivery

This paper describes VLP/lentiviral delivery of Cas9 RNPs for CAR T cell manufacturing, relevant as a general gene-editing delivery platform but not tied to SAMHD1 correction, myeloid tropism, or precision missense correction like prime editing.
DOI: 10.1016/j.omta.2026.201809

Prime Editing Mediated Generation and Correction of the mdx5cv Mutation Restores Dystrophin Expression in Myoblasts (from Muscular dystrophy/gene therapy)
A. Siddika; F. Husseiny; J. Rousseau; J. Tremblay — International Journal of Molecular Sciences 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This paper demonstrates a prime editing correction platform in muscle cells for DMD, technically relevant to gene correction methodology but not targeting immune/myeloid cells or the SAMHD1 pathway.
DOI: 10.3390/ijms27156927

Mitochondrial transfer in the tumor microenvironment: mechanisms, immunometabolic consequences, and therapeutic implications. (from Oncology/tumor immunology)
Feng Sijia; Hu Yanan; Li Shuqing; Chang Yuqiao; Li Zhenwei — Critical reviews in oncology/hematology 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, other

Discusses mtDNA-driven cGAS-STING/NLRP3/TLR9 signaling and mitochondrial transfer in tumor immunometabolism, tangentially touching core pathways but in an oncology tumor-microenvironment context unrelated to SAMHD1 mechanism.
DOI: 10.1016/j.critrevonc.2026.105530

Signaling pathways and ion channels in osteoarthritis: a review of recent advances (from Orthopedics/Rheumatology (osteoarthritis))
Xi Liu; Niqing Xiao; Qiumei He; Kuanmeng Chi; Hongting Lu — Frontiers in Immunology 2026
Score: 3/10 | Pathways: NLRP3, cGAS-STING, NF-kB-IKK

This paper covers NF-κB, cGAS-STING, and NLRP3 signaling but in the context of osteoarthritis mechanobiology, with no connection to SAMHD1, interferonopathy, or the family phenotype spectrum.
DOI: 10.3389/fimmu.2026.1823905

Shi Pi Shu Gan Formula Prevents and Treats Sequelae of Pelvic Inflammatory Disease by Regulating PKA-CREB-Yap1 Signaling through the mtDNA/cGAS/STING Network. (from Traditional Chinese Medicine / Gynecology)
Mi Yuyang; He Haiqing; Huang Yefang; Huang Li; Li Maoya — 2026
Score: 3/10 | Pathways: cGAS-STING

Demonstrates mtDNA-cGAS-STING pathway activation and mitophagy regulation in a rat model of pelvic inflammatory disease using a TCM herbal formula, sharing core mechanistic pathway but unrelated to SAMHD1 or the family phenotype spectrum.
DOI: 10.2174/0118715303458984260714211650

Respiratory syncytial virus inhibits type I interferon signaling to maintain HLA-DM expression in CD1c+ dendritic cells. (from Virology/Dendritic cell immunology)
Ong Weiyee; Hopkins Richard Anthony; Yang Enjun; Novita; Talib Najwa — iScience 2026
Score: 3/10 | Pathways: JAK-STAT, other

This paper concerns TBK1-dependent Type I IFN signaling regulating HLA-DM/antigen presentation in RSV-infected dendritic cells, touching on IFN-I pathway machinery but not on SAMHD1, mitochondrial dysfunction, or inflammasome mechanisms central to the disease profile.
DOI: 10.1016/j.isci.2026.116736

Comparative Analysis of LPS/IFN-γ and LPS/ATP-Induced Inflammatory Models in BV2 Microglia. (from Neuroinflammation/microglial pharmacology)
Zhang Xinfeng; Lian Zhuo; Lei Sijie; Yi Tanhui; Zhao Shuyin — Neurochemical research 2026
Score: 3/10 | Pathways: NLRP3

This paper compares in vitro microglial inflammation models using NLRP3/IL-1beta and NO/TNF-alpha readouts but does not involve SAMHD1, cGAS-STING, mitochondrial dNTP transport, or any disease-specific mechanism relevant to the profile.
DOI: 10.1007/s11064-026-04853-0

Pathway Coverage This Week

  • cGAS-STING: 11 papers
  • treatment-target: 9 papers
  • NLRP3: 7 papers
  • other: 4 papers
  • gene-therapy-delivery: 4 papers
  • mito-ROS-NF-kB: 3 papers
  • NF-kB-IKK: 3 papers
  • clinical-phenotype: 3 papers
  • POLG-mtDNA: 3 papers
  • VDAC1: 2 papers
  • JAK-STAT: 2 papers
  • prime-editing: 2 papers
  • pregnancy-fetal: 1 papers
  • IRF7-metabolic: 1 papers
  • AGS-spectrum: 1 papers
  • dNTPase: 1 papers

SAMHD1 Research Digest — 2026-08-02

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 24 papers evaluated | 2 high-relevance (≥7) | 13 medium (5–6) | 9 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells to induce TFH differentiation 2253320 (from Rheumatology/Autoimmunity)
Hongxu Xian; Michael Karin — The Journal of Immunology 2026
Score: 8/10 | Pathways: NLRP3, cGAS-STING, IRF7-metabolic, POLG-mtDNA, NF-kB-NLRP3-priming, clinical-phenotype

Demonstrates that oxidized mtDNA released via NLRP3/caspase-1/gasdermin-D drives pDC-mediated IL-1β and IFN-α signaling to promote TFH differentiation and autoantibody-driven autoimmunity, directly reinforcing the ox-mtDNA-NLRP3-IFN convergence central to the SAMHD1 A565T mechanism and its autoimmune/rheumatologic phenotype spectrum.
DOI: 10.1093/jimmun/vkag141.168

Pannexin1 promotes cellular senescence by triggering mtDNA release to activate the cGAS-STING pathway. (from Nephrology (acute kidney injury/chronic kidney disease and cellular senescence))
Li Jiaqi; Zhao Xin; Shen Yanting; Huang Liuwei; Guo Jie — 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, VDAC1, treatment-target

This paper demonstrates mtDNA release via mPTP/BAX activating cGAS-STING to drive NF-κB-mediated SASP and IRF3 interferon output, directly paralleling the BLUE/Loop A mechanism (mtDNA escape → cGAS → STING → IFN-I plus NF-κB crosstalk) central to the SAMHD1 interferon-mitochondrial syndrome, though in a renal senescence rather than SAMHD1 context.
DOI: 10.1016/j.bbadis.2026.168388

🟡 Medium Relevance (Score 5–6)

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

Diazonium-Enabled Post-Synthetic Construction of Enantiomeric Single-Atom Nanoagents Used for Alzheimer's Disease Treatment. (from Neurology/Nanomedicine)
Ya Junlin; Liu Mengmeng; Ji Yanjun; Tong Zhibo; Luo Bin — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mtDNA leakage-driven cGAS-STING activation in neuroinflammation and a nanoagent therapeutic strategy directly targeting this core pathway, relevant to the interferon-mitochondrial mechanism though not SAMHD1-specific.
DOI: 10.1002/smll.74610

The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets. (from Cardiology)
Rong Jiaxiang; Wang Zhen; Lin Xiaoxiao; Lei Ziwen; Huang Qianqian — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target, clinical-phenotype

This review synthesizes cGAS-STING, NLRP3, and mitochondrial DAMP-driven inflammatory circuits in cardiovascular disease that mechanistically overlap with the SAMHD1-driven interferon-mitochondrial pathways implicated in the family's cardiac and metabolic phenotypes, though it does not address SAMHD1 directly.
DOI: 10.1002/mco2.70878

Mito-TEMPO attenuates LPS-induced acute lung injury accompanied by ferroptosis suppression and reduced HSP90-STING association. (from Pulmonology/critical care)
Yao Yun; Guo Wei; Tian Yujia; Zeng Lisheng; Xia Xin — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial ROS scavenging (Mito-TEMPO) disrupting STING signaling (via HSP90-STING/TBK1-IRF3) and downstream ferroptosis in acute lung injury, directly paralleling the BLUE pathway's cGAS-STING-IFN axis and mito-ROS/NF-kB crosstalk relevant to interferonopathy-driven mitochondrial damage.
DOI: 10.1016/j.intimp.2026.117210

Modulation of Toll-like receptor driven monocyte activation by JAK-STAT inhibitors in people with HIV. (from Infectious disease/HIV immunology)
Camard Marion; Plaçais Léo; Bitu Marie; Mouanga Christelliah; Bourdic Katia — AIDS (London, England) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates JAK-STAT inhibitors (baricitinib, a drug listed as therapeutically relevant) suppressing TLR-driven IFN-I monocyte activation, directly supporting the RED pathway/IFN-JAK-STAT axis therapeutic rationale relevant to SAMHD1 interferonopathy management.
DOI: 10.1097/QAD.0000000000004530

The Autophagy-Inflammasome Axis as a Molecular Switch: From Persistent Inflammation to Vascular Remodeling in IVIG-Resistant Kawasaki Disease. (from Pediatric rheumatology/cardiology (Kawasaki disease vasculitis))
Zhang Rong; Zhang Jiaqi; Yang Yanzhi; Wang Ya; Cao Haijun — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, clinical-phenotype

Discusses mitophagy dysfunction driving cGAS-STING/NLRP3 inflammasome activation and IL-1β signaling in a pediatric vasculitis, mechanistically parallel to the SAMHD1 interferon-mitochondrial-inflammasome axis but in a distinct clinical context.
DOI: 10.3390/ijms27146405

Rocket-Inspired Sequentially Targeted Nanotherapeutics for Mitochondrial Regulation and Inflammatory Reprogramming in Ischemic Stroke. (from neurology/nanomedicine)
Bai He; Yong Zihao; Li Yang; Chen Qingmin; Liu Yong — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates a Drp1/mtDNA/cGAS-STING axis driving neuroinflammation with a mitochondrial-targeted nanotherapeutic, mechanistically adjacent (mtDNA release/cGAS-STING) though not SAMHD1-specific and in a different disease context (stroke).
DOI: 10.1002/advs.76859

Research Progress on Regulating Neuroinflammation After Spinal Cord Injury by Targeting the cGAS-STING Pathway. (from Neurosurgery/Spinal cord injury)
Xu Nanjian; Ma Weihu; Dong Weixin; Yu Liang — Neuromolecular medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Reviews cGAS-STING/mtDNA-driven NLRP3 activation and pyroptosis in neuroinflammation, mechanistically overlapping with Loop A/B and NLRP3 priming/activation core to the SAMHD1 syndrome, though in a spinal cord injury context rather than SAMHD1 disease.
DOI: 10.1007/s12017-026-08938-5

Köhlmeier-Degos disease is an interferonopathy characterized by type I and II interferon-driven inflammatory vasculopathy. (from Dermatology/Vasculopathy (rare disease immunology))
Cudrici Cornelia D; Goel Shubham; Sakamoto Keiko; Jin Seon-Pil; Sekiguchi Akiko — Cell reports. Medicine 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype

This paper demonstrates a type I/II interferonopathy vasculopathy responsive to JAK inhibition (ruxolitinib), directly paralleling the IFN-I-driven mechanism and JAK inhibitor therapeutic strategy relevant to SAMHD1-mediated interferonopathy, though it does not involve SAMHD1 or mitochondrial dNTP pathways.
DOI: 10.1016/j.xcrm.2026.102947

Exercise alleviates neuroinflammation and cognitive decline in aged mice via hepatic FGF21-driven microglial mitophagy. (from Neurology/Exercise Physiology)
Li Pengda; Wu Tao; Chen Mengjie; Wang Nan; Jia Xiaopeng — 2026
Score: 6/10 | Pathways: cGAS-STING, mTOR-lysosomal, treatment-target

The paper demonstrates cytosolic mtDNA accumulation driving cGAS-STING neuroinflammation and its reversal via AMPK-TFEB-mediated mitophagy, directly paralleling the BLUE loop and mitophagy-block mechanisms central to the SAMHD1 syndrome, though in an aging/exercise context rather than SAMHD1-specific.
DOI: 10.1016/j.bbi.2026.106935

Phase-dependent dynamics of circulating cell-free mitochondrial DNA reflect distinct immunometabolic states (from Infectious disease/tropical medicine (tuberculosis) and pediatric cardiac surgery)
Karen Alessandra Rodrigues; Emilly Henrique dos Santos; Gabriel Acca Barreira; M — Revista do Instituto de Medicina Tropical de São Paulo 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, POLG-mtDNA, clinical-phenotype

Circulating cell-free mtDNA as a DAMP linking mitochondrial damage to innate immune activation is directly relevant to the BLUE/PURPLE loop mechanisms (VDAC1-mediated mtDNA release, NLRP3 activation) even though SAMHD1 is not studied.
DOI: 10.1590/S1678-9946202668048

Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model. (from Cardiology/metabolic physiology)
Mills Aimee R; de Souza Antonio; Pham Toan; Mugisho Odunayo O — Experimental physiology 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target, other

Demonstrates a mitochondrial-derived peptide suppressing NLRP3 inflammasome activation (with uric acid correlation) in a diabetic cardiac model, relevant as an adjacent NLRP3/mitochondrial dysfunction mechanism and potential therapeutic strategy but not tied to SAMHD1/interferon pathways.
DOI: 10.1113/EP093714

Microglial immunometabolic reprogramming in Alzheimer's disease: From mitochondrial dysfunction and redox imbalance to NLRP3 inflammasome-driven neuroinflammation. (from Neurology/Alzheimer's disease neuroimmunology)
Li Siyu; Jin Juntao; Liu Yingying; Yuan Jing; Dong Yuhan — Journal of Alzheimer's disease : JAD 2026
Score: 5/10 | Pathways: NLRP3, mito-ROS-NF-kB, other

This review addresses mitochondrial dysfunction, oxidized mtDNA, and NLRP3 inflammasome activation in AD microglia, mechanistically overlapping with the PURPLE/GOLD/mito-ROS-NF-kB streams but in a neurodegenerative rather than SAMHD1-interferonopathy context.
DOI: 10.1177/13872877261469862

Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression. (from Hematology/gene therapy engineering)
Bandala-Sanchez Esther; Petley Emma V; Ramsay Kerry; Hilton Adrienne; White Chri — Blood 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery, treatment-target

Demonstrates multiplex prime editing to correct pathogenic immune-dysregulation variants and engineer drug-resistant T-cells, directly relevant as a translational platform for future correction of heterozygous missense mutations like SAMHD1 A565T in immune/myeloid cells, though not disease-specific.
DOI: 10.1182/blood.2026033156

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

FROM ONE-SIZE-FITS-ALL TO ON-DEMAND: PERSONALIZED CRISPR GENE EDITING FOR RARE GENETIC LIVER DISEASES. (from Hepatology/gene therapy)
Anh Tuan Quan — Clinics and research in hepatology and gastroenterology 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This review covers CRISPR/base/prime editing and LNP delivery platforms for monogenic liver diseases, offering only general technological overlap with future SAMHD1 correction strategies but no direct SAMHD1, interferon, or mitochondrial pathway relevance.
DOI: 10.1016/j.clinre.2026.102892

CRISPR application in hematological disorders: from bench to bedside. (from Hematology/gene therapy)
Ladisa Francesco; Morelli Eugenio; Soncini Debora; Garibotto Matteo; Munshi Nikh — Blood advances 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general review of CRISPR/base/prime editing in hematologic diseases with no SAMHD1, interferon, or mitochondrial pathway content, only tangentially relevant as background on editing modalities that could theoretically correct a SAMHD1 missense variant in hematopoietic/myeloid cells.
DOI: 10.1182/bloodadvances.2025017417

Dual Roles of Free Fatty Acids in Gout Pathogenesis: Inflammatory Drivers and Metabolic Mediators. (from Rheumatology/metabolic lipidology)
Lin Na; Shao Chongyu — International journal of rheumatic diseases 2026
Score: 4/10 | Pathways: NLRP3, urate-NLRP3

Discusses FFA-driven NLRP3 activation and MSU crystal gout mechanisms which touch the GOLD pathway (uric acid-NLRP3 axis) but lacks any SAMHD1, interferon, or mitochondrial dNTP connection.
DOI: 10.1111/1756-185x.70799

Extracellular vesicle-mediated immune crosstalk in rheumatoid arthritis synovium: mechanistic insights and translational challenges (from Rheumatology/EV biology)
Feng Luo; Xuemei Yuan; Heng Zhou; Qiuyi Wang; Changming Chen — Frontiers in Immunology 2026
Score: 4/10 | Pathways: NF-kB-IKK, JAK-STAT, cGAS-STING, clinical-phenotype

This review discusses RA synovial EV-mediated NF-κB/JAK-STAT/cGAS-STING signaling, which touches on core interferonopathy pathways and matches the RA family phenotype, but has no direct SAMHD1, mitochondrial dNTP, or NLRP3 mechanistic link.
DOI: 10.3389/fimmu.2026.1891984

Rutin as a multi-target anti-inflammatory phytochemical in arthritic disorders: pharmacological mechanisms and therapeutic potential. (from Rheumatology/phytopharmacology)
Nazir Muhammad Muzammil; Ashraf Asma — Inflammopharmacology 2026
Score: 3/10 | Pathways: NLRP3, urate-NLRP3, NF-kB-IKK, JAK-STAT

This phytochemical review on rutin in arthritis touches tangentially on NLRP3, NF-κB, JAK-STAT, and urate pathways relevant to the GOLD stream and RA/gout family phenotypes, but has no connection to SAMHD1, interferon signaling, or mitochondrial mechanisms.
DOI: 10.1007/s10787-026-02351-x

Nanobody-STING Agonist Reprogram the Tumor Microenvironment and Improve Adoptive Cell Therapy for Solid Tumors 2309144 (from Oncology/immunotherapy)
Neil C. Chada; Alex Lee; H. Frank; Dawn K. Oh; Hannah Ki — The Journal of Immunology 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This paper uses a STING agonist to boost tumor immunity in oncology/immunotherapy context, tangential to the SAMHD1 disease's constitutive STING activation pathway but not addressing interferonopathy, SAMHD1, or mitochondrial dysfunction mechanisms.
DOI: 10.1093/jimmun/vkag141.1501

ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing (from chemical biology/cancer pharmacology)
Tse Jason; Brothers William; Hayward Rachel; Barbas Sabrina; Sheng Kai — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing

This paper describes a general prime-editing-based functional genomics platform for covalent ligand characterization in cancer cell lines, unrelated to SAMHD1 biology, interferonopathy, or immune/myeloid gene correction strategies.
DOI: 10.64898/2026.07.28.741261

In vivo reconstruction of the cell lineage history of a developing mouse with DNA Typewriter, from zygote to late organogenesis (from Developmental biology/genomics)
Yu Qi; Kim Haedong; Seidel Sophie; Acosta-Clark James; Martin Beth — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing

This paper demonstrates a prime editing-based lineage tracing technology in mouse embryos, which is only tangentially relevant as a general prime editing methodology advance rather than a myeloid/immune-targeted gene correction strategy applicable to SAMHD1 A565T.
DOI: 10.64898/2026.07.29.741625

Poly(I:C) and QS-21 combination suppresses breast tumor growth and metastasis by repolarizing tumor associated macrophages to anti-tumor macrophages. (from oncology/tumor immunology)
Zheng Haoxin; Jin Yanyan; Wang Zixuan; Yang Guang; Li Jianming — European journal of pharmacology 2026
Score: 3/10 | Pathways: JAK-STAT, cGAS-STING, treatment-target

This oncology-immunotherapy paper uses TBK1-IRF3/type I IFN and JAK-STAT signaling in macrophages, which overlaps mechanistically with the interferonopathy axis but is applied to TNBC immunotherapy rather than SAMHD1 biology.
DOI: 10.1016/j.ejphar.2026.179203

Pathway Coverage This Week

  • treatment-target: 14 papers
  • cGAS-STING: 12 papers
  • NLRP3: 9 papers
  • clinical-phenotype: 7 papers
  • JAK-STAT: 5 papers
  • prime-editing: 5 papers
  • NF-kB-IKK: 4 papers
  • mito-ROS-NF-kB: 3 papers
  • other: 3 papers
  • urate-NLRP3: 3 papers
  • gene-therapy-delivery: 3 papers
  • POLG-mtDNA: 2 papers
  • VDAC1: 2 papers
  • IRF7-metabolic: 1 papers
  • NF-kB-NLRP3-priming: 1 papers
  • AGS-spectrum: 1 papers
  • mTOR-lysosomal: 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

SAMHD1 Research Digest — 2026-07-26

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 31 papers evaluated | 5 high-relevance (≥7) | 16 medium (5–6) | 10 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Modeling calcific aortic valve disease with engineered human valve tissues identifies SAMHD1 as a therapeutic target. (from Cardiology/bioengineering (tissue engineering and valvular calcification))
Meng Xiangfu; Zhou Qian; Zhu Zijin; Qiao Weihua; Geng Bingchuan — Biomaterials 2026
Score: 7/10 | Pathways: treatment-target, clinical-phenotype, other

This paper identifies SAMHD1 as a novel therapeutic target in calcific aortic valve disease via WGCNA-driven small-molecule inhibition, extending SAMHD1's disease relevance beyond interferonopathy into a cardiovascular/osteogenic context pertinent to potential cardiac phenotypes in the family.
DOI: 10.1016/j.biomaterials.2026.124432

The mitochondrial DNA signal in rheumatoid arthritis: From metabolic victim to inflammatory driver. (from Rheumatology)
Zhang Ruoyi; Song Zhijie; Xin Qimeng; Xing Wenbin; Zhang Wenlan — Biochemical and biophysical research communications 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, clinical-phenotype, treatment-target

Reviews the mtDNA damage-release-cGAS/STING-NLRP3 axis driving RA inflammation, mechanistically parallel to the purple/blue loops in the SAMHD1 syndrome and directly relevant to the family's rheumatoid arthritis phenotype.
DOI: 10.1016/j.bbrc.2026.154304

Case of Aicardi-Goutières syndrome diagnosed in adulthood on whole-genome sequencing. (from Neurology/Genetics)
Cobb Lewis; Kumar Jayant; Roy Amit; Walsh Sarah; Sheerin Una-Marie — BMJ neurology open 2026
Score: 7/10 | Pathways: AGS-spectrum, cGAS-STING, JAK-STAT, treatment-target, clinical-phenotype

This adult-diagnosed ADAR-related AGS case with atypical presentation, cardiac calcification, and baricitinib consideration directly parallels the type I interferonopathy spectrum and JAK inhibitor treatment strategy relevant to SAMHD1-driven disease.
DOI: 10.1136/bmjno-2025-001407

HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway. (from Virology/hematology (HTLV-1-associated leukemia and neuroinflammatory disease))
Mohanty Suchitra; Suklabaidya Sujit; Mnatsakanyan Nelli; Jacobson Steven; Harhaj — Autophagy 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, NF-kB-IKK, treatment-target

This paper demonstrates PINK1-PRKN-dependent mitophagy (via NEMO/IKK interaction) suppressing cGAS-STING1-driven type I interferon activation in a viral infection context, directly paralleling the mitophagy-block/IFN-I-amplification mechanism central to the SAMHD1 syndrome model (RED/BLUE loops) even though the driver here is HTLV-1 Tax rather than SAMHD1 dysfunction.
DOI: 10.1080/15548627.2026.2707897

Type I interferonopathies: 15 years after the concept-news and views. (from Rheumatology)
S. Khaldi-Plassart; I. Melki; M. Frémond — Current opinion in rheumatology 2026
Score: 7/10 | Pathways: cGAS-STING, AGS-spectrum, treatment-target, clinical-phenotype, JAK-STAT

This review covers type I interferonopathy mechanisms (STING/IFNAR signaling, TLR pathways, clinical penetrance variability, JAK inhibitor therapeutics) directly relevant to the SAMHD1-driven IFN-I overproduction and AGS-spectrum disorder underlying the family syndrome, though it does not address SAMHD1 specifically.
DOI: 10.1097/BOR.0000000000001179

🟡 Medium Relevance (Score 5–6)

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

Fibroblast S1PR2 Amplifies NLRP3 Inflammasome Activation Under Pressure Overload. (from Cardiology)
Zhou Caixia; Liu Zhihao; Wang Zhiru; Cui Zekun; Wang Qian — Hypertension (Dallas, Tex. : 1979) 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial damage (DRP1 fission, mitophagy suppression) driving mtDNA leakage and NLRP3 activation, mechanistically parallel to the SAMHD1 mitochondrial-inflammasome axis though in cardiac fibroblasts rather than SAMHD1-deficient immune cells.
DOI: 10.1161/HYPERTENSIONAHA.126.27475

Isoalantolactone targets NLRP3 to disrupt NLRP3-NEK7 interaction and suppress inflammasome activation. (from pharmacology/drug discovery)
Shi Yuanfang; Zhu Xiaoyun; Sun Meng; Yang Yang; Lin Siwei — Biochemical pharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

This paper identifies a small-molecule NLRP3 inhibitor effective against MSU-induced gout and MASLD, directly relevant to the GOLD pathway (dGTP→uric acid→MSU→NLRP3) and offering a potential therapeutic candidate for the syndrome's inflammasome-driven pathology.
DOI: 10.1016/j.bcp.2026.118165

Interferon-related gene expression defines disease activity, organ involvement and treatment response in juvenile dermatomyositis. (from Pediatric rheumatology (juvenile dermatomyositis))
Codes-Méndez Helena; Cuyx Senne; Syntakas Aris E; Barmpakou Afroditi; Moraitis E — Rheumatology (Oxford, England) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates type-I interferon-related gene expression (ISGs, IFI27, IFI44L, RSAD2) as biomarker of disease activity and JAK inhibitor (baricitinib) response, directly reinforcing the IFN-I/JAK-STAT arm of the interferonopathy mechanism relevant to SAMHD1 pathway and treatment translation, though not SAMHD1-specific.
DOI: 10.1093/rheumatology/keag384

Glycerol-3-Phosphate Attenuates Hypoxic-Ischemic Brain Injury via Modulation of Microglia-Mediated Neuroinflammation. (from Neurology/perinatal neonatology)
Qin Dani; Lei Yong; Le Meini; Cheng Mengke; Zhao Yingmin — Neurochemical research 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, mito-ROS-NF-kB

Demonstrates cGAS-STING-TBK1-NF-kB axis driving microglial neuroinflammation and mitochondrial dysfunction, directly relevant to the same core pathway implicated in the SAMHD1 A565T interferon-mitochondrial syndrome, with therapeutic implications for neuroinflammatory phenotypes seen in the family (AuDHD, ME/CFS-like fatigue).
DOI: 10.1007/s11064-026-04848-x

Aspirin Inhibits the cGAS-STING Signaling Pathway to Ameliorate the Development of Aortic Aneurysm and Dissection. (from Vascular surgery/cardiology (aortic aneurysm and dissection))
Zeng Yi-Fan; Wang Qiu-Guo; Qi Zhen; Li Jing-Yu; Duan Zhi-Cheng — Arteriosclerosis, thrombosis, and vascular biology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates a novel cGAS-STING axis (via cGAS acetylation) driving mitochondrial/ferroptotic vascular pathology and its pharmacological inhibition by aspirin, directly relevant to the Blue loop mechanism though in a cardiovascular rather than immune context.
DOI: 10.1161/ATVBAHA.126.324930

Single-Cell Analysis of Residual Esophageal Squamous Cell Carcinoma After Neoadjuvant Immunochemotherapy Reveals TFAM-Mediated Immunoregulation in Dendritic Cells. (from Oncology (esophageal squamous cell carcinoma immunotherapy))
Chen Linyan; Feng Tang; Zhou Jianfeng; Zeng Hao; Lai Yutian — Cancer research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

This paper demonstrates TFAM deficiency in dendritic cells activating the STING-TBK1-IRF3 pathway to promote anti-tumor immunity, directly relevant to the mitochondrial-cGAS-STING-IFN-I axis central to the SAMHD1 mechanism though in an oncologic rather than interferonopathy context.
DOI: 10.1158/0008-5472.CAN-25-4738

Stub1 promotes chaperone-mediated autophagy to suppress antiviral immunity. (from Virology/cell biology (autophagy regulation))
Liu Hongyang; Huang Li; Weng Changjiang — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target

This paper describes a novel TBK1 degradation pathway (CMA via Stub1) that directly regulates the cGAS-STING-TBK1-IFN-I axis central to the SAMHD1 mechanism, relevant to interferonopathy modulation though not SAMHD1-specific.
DOI: 10.1080/15548627.2026.2667376

Dual-regulation of mitophagy and cytosolic mtDNA-induced inflammation for the treatment of inflammatory bone loss. (from orthopedics/bone regeneration)
Zheng Kaiwen; Che Benchi; Cui Yongzhi; Yang Han; Xiang Yu — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target, clinical-phenotype

Directly models the mtDNA-cGAS-STING-inflammation-mitophagy (PINK1) axis central to the BLUE/RED streams and demonstrates a dual STING/PINK1 exosome therapeutic, relevant to osteoporosis noted in family phenotype tracking though not SAMHD1-specific.
DOI: 10.1016/j.freeradbiomed.2026.07.031

Tumor microenvironment-responsive manganese nanoplatform amplifies cGAS-STING via metabolic-metal synergy for immunotherapy. (from Oncology/nanomedicine)
Zhou Yanlin; Wu Ziyi; Zheng Tao; Luo Shunhong; Zhang Lu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mitochondrial fragmentation-driven mtDNA leakage activating cGAS-STING (mirroring the BLUE/VDAC1 loop) in an oncology nanomedicine context, offering mechanistic and therapeutic parallels though not SAMHD1-specific.
DOI: 10.1016/j.jconrel.2026.115197

Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis. (from Orthopedics/Nanomedicine)
Li Tiancheng; Zheng Ao; Zhu Cheng; Li Yixin; Yang Zitong — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates a nanozyme therapeutic that restores mitophagy and blocks mtDNA-driven cGAS/STING inflammation, directly reinforcing the disease model's Loop A mechanism though in an unrelated joint disease context.
DOI: 10.1016/j.bioactmat.2026.07.010

Engineering-Modulated Molybdenum Enzymes Strategy for Tumor-Specific Metabolic-Immunotherapy. (from oncology/nanomedicine)
Pan Xiaoxiao; Pei Zifan; Wu Jie; Jiang Nan; Li Qian — 2026
Score: 6/10 | Pathways: cGAS-STING, urate-NLRP3, treatment-target

This oncology nanomedicine paper demonstrates mtDNA release activating cGAS-STING and purine metabolism driving uric acid elevation as an immune activator, mechanistically paralleling the PURPLE/GOLD and BLUE streams (dGTP-uric acid-MSU-NLRP3 and mtDNA-cGAS-STING) in the SAMHD1 syndrome despite being applied in a cancer immunotherapy context.
DOI: 10.1002/advs.76726

Phase-dependent dynamics of circulating cell-free mitochondrial DNA reflect distinct immunometabolic states (from Tropical medicine/infectious disease and pediatric cardiac surgery biomarker research)
Karen Alessandra Rodrigues; Emilly Henrique dos Santos; Gabriel Acca Barreira; M — Revista do Instituto de Medicina Tropical de São Paulo 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, treatment-target, clinical-phenotype

Circulating cell-free mtDNA as a DAMP driving innate immune activation is directly relevant to the BLUE/PURPLE mitochondrial escape and NLRP3 activation loops central to the SAMHD1 interferon-mitochondrial syndrome, though it does not address SAMHD1 itself.
DOI: 10.1590/s1678-9946202668048

Severe Antenatal Presentation of a Novel Dnase2 Mutation in a Preterm Omani Neonate: Expanding the Clinical Spectrum of an Ultra-Rare Interferonopathy (from Neonatology/Pediatric Genetics)
Ruqaiya Al Jashmi; Marya Al Barumi; S. Al Abrawi; Alyaa Al Mughairy; Aiman Al Ja — Cureus 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, clinical-phenotype, pregnancy-fetal, treatment-target

DNASE2 deficiency is a type I interferonopathy in the same AGS-spectrum family of diseases as SAMHD1 mutations, sharing cGAS-STING-driven IFN-I pathology and JAK inhibitor responsiveness, with fetal/neonatal presentation relevant to the pregnancy-interferonopathy phenotype tracking axis.
DOI: 10.7759/cureus.111043

Sex-specific differences of amlexanox in a mouse model for atherosclerosis and MASLD. (from Cardiometabolic/hepatology research on IKKε inhibition)
Mungo Eleonora; Haß Michelle; Benning Denis; Schmid Tobias; Kuntschar Silvia — Molecular metabolism 2026
Score: 5/10 | Pathways: NF-kB-IKK, clinical-phenotype

IKKε (a kinase explicitly named in the NF-κB crosstalk mechanism as dual NF-κB/IRF3 activator) is targeted pharmacologically here, showing sex-specific metabolic/inflammatory effects on MASLD and atherosclerosis, relevant background to the IKKβ/IKKε axis but without SAMHD1 or interferon pathway data.
DOI: 10.1016/j.molmet.2026.102426

Editing Around the Target: Epitope Engineering to Protect Stem Cell Grafts. (from Gene therapy/hematology-oncology)
Baek Joanne; Casirati Gabriele; Genovese Pietro; Gill Saar I — Blood advances 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews base/prime editing epitope engineering in HSPCs, relevant as a generic delivery/correction platform potentially applicable to correcting SAMHD1 missense variants in myeloid cells but not disease-specific.
DOI: 10.1182/bloodadvances.2025018227

Efficient CRISPR/Cas9-mediated homology independent sequence replacement in vivo and non-dividing primary cells (from genome editing / gene therapy engineering)
Dang Tu Ngoc; Roman Alexandra; Zimmer Anja; Lebedin Mikhail; Bahry Ella — preprint (preprint) 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

This paper describes a novel homology-independent CRISPR/Cas9 sequence replacement platform (REPLACE) using eVLP/AAV delivery in non-dividing cells, relevant as a general gene correction strategy applicable to correcting missense variants like SAMHD1 A565T though not directly tested on it.
DOI: 10.64898/2026.07.24.740048

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Alopecia areata: Mechanisms, targeted therapies, and translational challenges. (from Dermatology)
Kumar Virender; Sahoo Saurabh; Kumar Pawan — Current opinion in pharmacology 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

AA pathogenesis and JAK inhibitor therapy (baricitinib) overlap mechanistically with the IFN-I/JAK-STAT axis relevant to SAMHD1 interferonopathy, but the paper is otherwise unrelated to SAMHD1 or mitochondrial-inflammasome mechanisms.
DOI: 10.1016/j.coph.2026.102635

Gene therapy approaches for inborn errors of immunity: from bench to bedside. (from gene therapy/genetic medicine)
Dara Jasmeen; Booth Claire — Expert opinion on biological therapy 2026
Score: 4/10 | Pathways: gene-therapy-delivery

General review of gene therapy for inborn errors of immunity (retroviral, lentiviral, CRISPR, base/prime editing) provides background relevance to future correction strategies for SAMHD1 variants but has no disease-specific or mechanistic content.
DOI: 10.1080/14712598.2026.2710870

Mitochondrial stress-induced cuproptosis: a metabolic bridge to reprogramming the GBM immune microenvironment. (from Oncology (neuro-oncology/GBM immunotherapy))
Li Wenyang; Lv Yaqing; Wang Guanrong; Lan Xiaolei; Ren Leina — 2026
Score: 4/10 | Pathways: cGAS-STING, other

Discusses mtDNA release triggering cGAS-STING/type I IFN in GBM cuproptosis context, sharing a core mechanistic node but unrelated to SAMHD1 dNTPase biology or the family phenotype spectrum.
DOI: 10.1007/s13402-026-01254-x

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

General review of prime editing for neuropsychiatric monogenic disorders offers relevant delivery/technology context but no direct SAMHD1, immune, or mitochondrial pathway content and focuses on neurons rather than myeloid/immune cells.
DOI: 10.1002/nep3.70041

A poly(I:C)/QS-21-based in situ vaccine synergizes with anti-PD-1 therapy to overcome tumor immunoresistance. (from oncology/cancer immunotherapy)
Zhang Wenbo; Ni Xinrui; Zhuo Luoyi; Liu Jiangrui; Yang Guang — Cell reports. Medicine 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This oncology immunotherapy paper touches TBK1-IRF3-type I interferon axis (relevant pathway component) but in a tumor vaccine/anti-PD-1 context unrelated to SAMHD1 haploinsufficiency or the family's interferonopathy syndrome.
DOI: 10.1016/j.xcrm.2026.102932

Gene/Genome Editing in Cardiovascular Biology and Disease. (from Cardiology/gene therapy)
Verma Tushar; Singh Ravi Pratap; Chaudhary Mahima; Sharma Pramod Kumar; Kumar Dh — Current gene therapy 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general cardiovascular gene-editing review with no connection to SAMHD1, interferon-mitochondrial mechanisms, or myeloid/immune cell editing relevant to the family syndrome.
DOI: 10.2174/0115665232453929260206091608

Mitochondrial Communication Networks in the Bone Microenvironment: From the Maintenance of Homeostasis to Translational Interventions for Bone Diseases. (from Orthopedics/bone biology)
Wang Wentao; Wang Kun; Wang Wenjing; Mu Xuan; Cheng Zhiquan — 2026
Score: 3/10 | Pathways: cGAS-STING, other

Bone microenvironment mitochondrial transfer review touches cGAS-STING/mtDNA release but is focused on osteoporosis/osteoarthritis biology largely tangential to SAMHD1 interferonopathy mechanism.
DOI: 10.1007/s12015-026-11190-w

An Insight into the cGAS-STING Pathway Modulation by Metal Complexes to Initiate Immunogenic Cell Death in Cancer. (from medicinal chemistry/oncology)
Shilpendu Ghosh; Sujato Mukherjee; Arindam Mukherjee — Journal of medicinal chemistry 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

Discusses cGAS-STING pathway modulation via metal complexes for cancer immunotherapy, mechanistically relevant to Loop A but focused on oncology drug design rather than SAMHD1 or the family syndrome.
DOI: 10.1021/acs.jmedchem.6c00727

Caloric restriction enhances radiosensitivity of colorectal tumors through the cGAS-STING pathway activation. (from Oncology/radiation biology)
Li-Li Zhang; Li-Qiang Qin; Li Ding; Wenyue Shan; Yu Zhao — Cancer & metabolism 2026
Score: 3/10 | Pathways: cGAS-STING

This paper studies cGAS-STING pathway activation via caloric restriction to enhance radiosensitivity in colorectal cancer, sharing a core pathway but in an oncology/radiotherapy context unrelated to SAMHD1 dysfunction, mitochondrial dNTP dysregulation, or the interferonopathy syndrome described.
DOI: 10.1186/s40170-026-00449-y

From convergence to an iterative Optimization-Circumvention-Collapse framework in CRISPR bioengineering (from bioengineering/education)
Federico Filippone-Thaulero — Journal of High School Science 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General theoretical review of CRISPR/base/prime editing trade-offs from a high school science journal, with no immune/myeloid cell specificity or SAMHD1 relevance beyond generic gene-editing correction strategy context.
DOI: 10.64336/001c.165176

Pathway Coverage This Week

  • treatment-target: 21 papers
  • cGAS-STING: 18 papers
  • clinical-phenotype: 9 papers
  • JAK-STAT: 6 papers
  • gene-therapy-delivery: 6 papers
  • prime-editing: 5 papers
  • other: 4 papers
  • NLRP3: 4 papers
  • AGS-spectrum: 3 papers
  • NF-kB-IKK: 3 papers
  • ISG15-mitophagy: 2 papers
  • mito-ROS-NF-kB: 2 papers
  • urate-NLRP3: 2 papers
  • POLG-mtDNA: 1 papers
  • VDAC1: 1 papers
  • pregnancy-fetal: 1 papers