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 papersNLRP3: 9 papersclinical-phenotype: 7 papersmito-ROS-NF-kB: 6 paperstreatment-target: 5 papersgene-therapy-delivery: 5 papersJAK-STAT: 4 papersNF-kB-IKK: 4 papersprime-editing: 4 papersdNTPase: 2 papersother: 2 papersAGS-spectrum: 1 papersISG15-mitophagy: 1 papersPOLG-mtDNA: 1 papersurate-NLRP3: 1 papersVDAC1: 1 paperspregnancy-fetal: 1 papers