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 paperstreatment-target: 9 papersNLRP3: 7 papersother: 4 papersgene-therapy-delivery: 4 papersmito-ROS-NF-kB: 3 papersNF-kB-IKK: 3 papersclinical-phenotype: 3 papersPOLG-mtDNA: 3 papersVDAC1: 2 papersJAK-STAT: 2 papersprime-editing: 2 paperspregnancy-fetal: 1 papersIRF7-metabolic: 1 papersAGS-spectrum: 1 papersdNTPase: 1 papers