{
  "edition": "2026-10-15",
  "window": "15 July–15 October 2026",
  "records": [
    {
      "id": "srsf1",
      "title": "Transcriptomic reprogramming screen identifies SRSF1 as a regulator of aging",
      "short": "A different route to cellular reprogramming",
      "date": "2026-10-14",
      "journal": "Nature Aging",
      "authors": "Alexandru M. Plesa, Sascha Jung, et al.",
      "doi": "10.1038/s43587-026-01234-8",
      "url": "https://www.nature.com/articles/s43587-026-01234-8",
      "countries": [
        "United States",
        "Spain",
        "Luxembourg"
      ],
      "region": "United States",
      "model": "Cells + animals",
      "kind": "Research paper",
      "outcome": "Preclinical benefit",
      "topic": "Cell identity",
      "image": 1,
      "access": "Publisher abstract and data-availability statement checked. Full text and underlying datasets were not independently audited.",
      "sample": "Mouse survival groups: 9–10 animals per group.",
      "finding": "An RNA-splicing regulator, SRSF1, emerged from a screen for more youthful transcriptional states. In human fibroblasts, increased expression reduced several senescence-associated features without an observed loss of cell identity. The authors also reported less frailty progression and a 14% extension of median lifespan in a small aged-mouse experiment.",
      "limit": "Cells in culture and a small mouse survival experiment are not evidence of human rejuvenation. Durability, dose control, cancer-related risks, and independent replication remain critical questions.",
      "question": "Can the functional effect be replicated in independent aged-cell systems while preserving cell identity?",
      "endpoint": "Cell-state signatures; senescence-associated features; mouse frailty and survival."
    },
    {
      "id": "mechanical-reactivation",
      "title": "Microfluidic Mechanical Reactivation of Senescent Stem Cells",
      "short": "Can mechanics restore cultured-cell function?",
      "date": "2026-09-09",
      "journal": "Small",
      "authors": "Soo Bin Jang, et al.",
      "doi": "10.1002/smll.75587",
      "url": "https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.75587",
      "countries": [
        "South Korea"
      ],
      "region": "South Korea",
      "model": "Cells + animals",
      "kind": "Research paper",
      "outcome": "Preclinical benefit",
      "topic": "Cell mechanics",
      "image": 6,
      "access": "Publisher abstract and disclosure excerpts checked. Full methods and raw data were not independently audited.",
      "sample": "Sample sizes were not extracted for this brief.",
      "finding": "Controlled microfluidic compression improved several features of late-passage stem cells: lower oxidative-stress and senescence-associated signals, improved proliferation, and retained stem-cell characteristics. The authors also reported better wound closure in vitro and tissue repair in preclinical experiments.",
      "limit": "The intervention processed cultured cells outside the body. It does not show that pressure, vibration, or massage rejuvenates a person. Manufacturing repeatability and long-term cell safety require separate study.",
      "question": "Does a reproducible mechanical processing window improve function without selecting an abnormal surviving subpopulation?",
      "endpoint": "Proliferation, identity markers, stress readouts, and preclinical repair."
    },
    {
      "id": "india-metformin",
      "title": "Metformin Therapy Increases Leukocyte Telomere Length, Telomerase Activity, and Longevity Gene Expression in Asian Indians with Prediabetes: A 24-Week Participant-Blind, Outcome-Assessor-Blinded Randomized Controlled Trial",
      "short": "A human biomarker signal from India",
      "date": "2026-09-03",
      "journal": "Mechanisms of Ageing and Development",
      "authors": "Surya Prakash Bhatt, Shivam Pandey, Anoop Misra",
      "doi": "10.1016/j.mad.2026.112241",
      "url": "https://pubmed.ncbi.nlm.nih.gov/42692117/",
      "countries": [
        "India"
      ],
      "region": "India",
      "model": "Human randomized trial",
      "kind": "Research paper",
      "outcome": "Biomarker signal",
      "topic": "Telomeres",
      "image": 14,
      "access": "Indexed PubMed/publisher abstract excerpts checked. Full text was not reviewed.",
      "sample": "127 randomized; 112 completed; adults aged 30–60 with prediabetes.",
      "finding": "In a 24-week placebo-controlled study with lifestyle counseling in both groups, the investigators reported larger changes in leukocyte telomere measurements with metformin, alongside changes in telomerase activity and SIRT1 expression.",
      "limit": "A change in a blood-cell biomarker is not a percentage reduction in a person’s age. The result applies to the studied population with prediabetes and needs longer, independent validation. It is not prescribing advice.",
      "question": "Do the measurements replicate with orthogonal assays and predict a meaningful functional benefit?",
      "endpoint": "Leukocyte telomere measurements, telomerase activity, and gene expression."
    },
    {
      "id": "microbiome-5avab",
      "title": "A geroprotective probiotic and its functional metabolite counteract inflammaging to extend healthspan",
      "short": "One microbe. One metabolite. Several questions.",
      "date": "2026-08-25",
      "journal": "Nature Aging",
      "authors": "Xiaoyong Lu, et al.",
      "doi": "10.1038/s43587-026-01181-4",
      "url": "https://www.nature.com/articles/s43587-026-01181-4",
      "countries": [
        "China"
      ],
      "region": "China",
      "model": "Human observation + animals",
      "kind": "Research paper",
      "outcome": "Preclinical benefit",
      "topic": "Microbiome",
      "image": 11,
      "access": "Publisher abstract checked. Full text and underlying cohort datasets were not independently audited.",
      "sample": "Multiple human cohorts and naturally aged mice; sample sizes not extracted.",
      "finding": "Bifidobacterium pseudocatenulatum and its metabolite 5-aminovaleric acid betaine were associated with aging in human observations. Intervention experiments in naturally aged mice reported improvements in gut function, inflammation, and functional measures; the metabolite reproduced part of the bacterial intervention’s effect.",
      "limit": "The human evidence was observational, not a rejuvenation treatment trial. Neither a generic probiotic nor ordinary betaine is interchangeable with the tested intervention.",
      "question": "Which effects require the organism, which require its metabolite, and which depend on the host’s starting microbiome?",
      "endpoint": "Human abundance associations; mouse intestinal, inflammatory, and functional outcomes."
    },
    {
      "id": "sphk2-blood-stem-cells",
      "title": "Ferroptotic stress promotes hematopoietic stem cell aging through S1P-dependent epigenetic and lipid remodeling",
      "short": "Protecting the blood-forming system",
      "date": "2026-08-24",
      "journal": "Blood",
      "authors": "Yijun Zhao, et al.",
      "doi": "10.1182/blood.2026034204",
      "url": "https://ashpublications.org/blood/article/doi/10.1182/blood.2026034204/570472/Ferroptotic-stress-promotes-hematopoietic-stem",
      "countries": [
        "China"
      ],
      "region": "China",
      "model": "Cells + animals",
      "kind": "Research paper",
      "outcome": "Preclinical benefit",
      "topic": "Lipid metabolism",
      "image": 16,
      "access": "Indexed publisher/PubMed excerpts checked. Full text was not reviewed.",
      "sample": "Aged human and mouse hematopoietic stem-cell systems; sizes not extracted.",
      "finding": "The study connects ferroptotic stress, lipid remodeling, and Sphk2 signaling to aging blood-forming stem cells. Inhibition of Sphk2 reduced damaging stress in the investigated cell systems and improved aspects of stem-cell function and immune balance in aged mice.",
      "limit": "Work involving human cells is not a clinical trial. A systemic intervention would require evidence about effects on other cell populations and normal immune function.",
      "question": "Can stress be reduced while preserving the normal functions of the blood and immune system?",
      "endpoint": "Stem-cell stress, function, lipid remodeling, and mouse immune balance."
    },
    {
      "id": "rentosertib-clocks",
      "title": "Integration of proteomic aging clocks in a phase 2a clinical trial supports simultaneous geroprotective assessment",
      "short": "When a younger clock may track disease recovery",
      "date": "2026-09-07",
      "journal": "Nature Biotechnology",
      "authors": "Alex Zhavoronkov, Fedor Galkin, et al.",
      "doi": "10.1038/s41587-026-03286-y",
      "url": "https://www.nature.com/articles/s41587-026-03286-y",
      "countries": [
        "China"
      ],
      "region": "China",
      "model": "Human trial reanalysis",
      "kind": "Research paper",
      "outcome": "Biomarker signal",
      "topic": "Measurement",
      "image": 18,
      "access": "Publisher abstract and selected main-text sections checked; no independent reanalysis.",
      "sample": "Secondary analysis of a previous 12-week phase 2a lung-disease trial.",
      "finding": "Six protein-based aging clocks were applied to samples from a rentosertib trial in idiopathic pulmonary fibrosis. The analysis reported shifts toward younger predicted ages in treated groups. This is a new 2026 analysis of an earlier clinical trial, not a newly completed general-aging trial.",
      "limit": "Changes associated with improvement of lung disease could not be cleanly separated from an aging-specific effect. Agreement among clocks does not establish whole-person rejuvenation.",
      "question": "Does the result persist after accounting for disease activity and validate against an independent functional endpoint?",
      "endpoint": "Proteomic aging-clock estimates in previously collected clinical samples."
    },
    {
      "id": "japan-nmn",
      "title": "Sustained NAD+ augmentation by high-dose nicotinamide mononucleotide supplementation in older adults: a 24-week randomized, double-blind, placebo-controlled trial",
      "short": "Target engagement is not the same as benefit",
      "date": "2026-09-25",
      "journal": "npj Aging",
      "authors": "Masaki Igarashi, Kyoko Naruse, Yuriko Takaoka, et al.",
      "doi": "10.1038/s41514-026-00482-7",
      "url": "https://www.nature.com/articles/s41514-026-00482-7",
      "countries": [
        "Japan"
      ],
      "region": "Japan",
      "model": "Human randomized trial",
      "kind": "Research paper",
      "outcome": "Null primary endpoint",
      "topic": "Mitochondria",
      "image": 2,
      "access": "Publisher abstract of accepted manuscript and funding details checked; full data not audited.",
      "sample": "Adults aged 65 and older; 24 weeks. Trial: jRCTs031220373.",
      "finding": "NMN increased blood NAD and related metabolites in a randomized placebo-controlled trial. It did not significantly improve the primary hearing outcome or measured physical-performance outcomes. Some exploratory changes did not remain significant after multiple-comparison correction.",
      "limit": "This is evidence of biochemical target engagement without demonstrated benefit on the primary functional endpoint. It does not establish that NMN can never help, or that it reverses human aging. Industry funding and material support were disclosed.",
      "question": "What functional endpoint, population, and duration would make a future study informative rather than merely biochemical?",
      "endpoint": "Blood NAD metabolites; hearing and physical-performance outcomes."
    },
    {
      "id": "neural-stem-conversion",
      "title": "Protracted Fate Acquisition and Epigenetic De-Aging During Induced Neural Stem Cell Conversion of Human Blood Cells",
      "short": "A younger molecular state—after an identity change",
      "date": "2026-10-03",
      "journal": "Aging Cell",
      "authors": "Lea Jessica Berg, Jana Franzen, et al.",
      "doi": "10.1111/acel.70751",
      "url": "https://onlinelibrary.wiley.com/doi/10.1111/acel.70751",
      "countries": [
        "Germany"
      ],
      "region": "Europe",
      "model": "Human cells in culture",
      "kind": "Research paper",
      "outcome": "Cell-state change",
      "topic": "Cell identity",
      "image": 8,
      "access": "Publisher abstract and selected introductory text checked. Full methods not audited.",
      "sample": "Blood-derived cells from donors spanning newborn to 101 years old.",
      "finding": "Conversion of blood-derived progenitors into induced neural stem cells was accompanied by extensive epigenetic age resetting. Both acquisition of the new identity and the molecular changes unfolded over time rather than happening immediately.",
      "limit": "The cells changed identity. This is not rejuvenation of an existing human brain, proof of preserved memories, or a demonstration of safe transplantation. An age signature and a functional neural cell are different validation targets.",
      "question": "Can the resulting cell population achieve stable, appropriate function and genomic safety over long follow-up?",
      "endpoint": "Epigenetic age measures and acquisition of neural stem-cell identity."
    },
    {
      "id": "targeted-liver-mrna",
      "title": "Enhanced liver regeneration via targeted mRNA delivery for partial in vivo reprogramming",
      "short": "Temporary instructions. A specific tissue.",
      "date": "2026-10-01",
      "journal": "Cell Reports Medicine",
      "authors": "Beom-Ki Jo, Young Seok Song, Woohyun Song, et al.",
      "doi": "10.1016/j.xcrm.2026.103084",
      "url": "https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00501-X",
      "countries": [
        "South Korea"
      ],
      "region": "South Korea",
      "model": "Animal intervention",
      "kind": "Research paper",
      "outcome": "Preclinical repair",
      "topic": "Delivery",
      "image": 10,
      "access": "Publisher metadata and indexed excerpts checked. Full text was not reviewed.",
      "sample": "Mouse models of acute liver injury; sample sizes not extracted.",
      "finding": "Liver-targeted lipid nanoparticles carrying reprogramming-factor mRNA enhanced regeneration in experimental acute liver injury. The work is relevant to control of where and for how long reprogramming instructions act.",
      "limit": "Recovery after acute injury is not reversal of normal aging. The finding is preclinical and does not establish safe human liver rejuvenation. Online publication is October 1; the issue date is later.",
      "question": "Can tissue specificity, reversibility, and long-term identity stability be demonstrated independently of acute injury recovery?",
      "endpoint": "Regeneration and recovery after experimental acute liver injury."
    },
    {
      "id": "longer-lipids",
      "title": "Longer lipids mark aging and constrain lifespan",
      "short": "The chemistry of membranes—not just the amount of fat",
      "date": "2026-10-06",
      "journal": "Nature Aging",
      "authors": "Weisha Li, Bauke V. Schomakers, et al.",
      "doi": "10.1038/s43587-026-01223-x",
      "url": "https://www.nature.com/articles/s43587-026-01223-x",
      "countries": [
        "Netherlands"
      ],
      "region": "Europe",
      "model": "Cross-species + worms",
      "kind": "Research paper",
      "outcome": "Preclinical benefit",
      "topic": "Lipid metabolism",
      "image": 5,
      "access": "Publisher abstract and affiliation information checked. Underlying lipidomics data not reanalyzed.",
      "sample": "Human, mouse, fly, and worm systems; lifespan intervention in worms.",
      "finding": "Longer fatty-acid chains in cellular lipids were associated with aging across several species. Reducing PLB1 activity in worms reversed the lipid-lengthening pattern and extended lifespan. Human genetic analyses added an association with frailty.",
      "limit": "The lifespan intervention was in worms. The study does not validate a dietary-oil choice or a human longevity treatment. A molecular remodeling pathway is not equivalent to changing dietary fat intake.",
      "question": "Which cell types depend on the remodeling pathway, and can functional benefits be separated from developmental effects?",
      "endpoint": "Lipid-chain composition; worm lifespan; human genetic associations."
    },
    {
      "id": "cardiolipin-muscle",
      "title": "Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor gamma",
      "short": "A membrane lipid connects to muscle function",
      "date": "2026-09-29",
      "journal": "Nature Aging",
      "authors": "Fabian Finger, Mikkel Frost, et al.",
      "doi": "10.1038/s43587-026-01227-7",
      "url": "https://www.nature.com/articles/s43587-026-01227-7",
      "countries": [
        "Denmark"
      ],
      "region": "Europe",
      "model": "Human observation + animals",
      "kind": "Research paper",
      "outcome": "Preclinical repair",
      "topic": "Mitochondria",
      "image": 13,
      "access": "Publisher abstract and selected main-text passages checked. Full methods and datasets not independently audited.",
      "sample": "Human muscle observations and genetically altered mouse models.",
      "finding": "The study links cardiolipin metabolism to aging-related muscle adaptations. In engineered mouse systems, loss of Crls1 reproduced aspects of mitochondrial dysfunction. Restoring Crls1 in adult deficient mice rescued cardiolipin metabolism and initiated recovery from the induced phenotype.",
      "limit": "Rescuing an engineered deficiency is not the same as rejuvenating normally aging humans. The distinction matters when judging both mechanism and expected benefit.",
      "question": "Does restoring this pathway improve normally aged tissue, beyond correcting the engineered deficiency?",
      "endpoint": "Cardiolipin metabolism, mitochondrial function, and muscle phenotype."
    },
    {
      "id": "ramanomics",
      "title": "RamanOmics decodes the spatial vibrational–molecular architecture of senescence in aging and repair",
      "short": "Seeing cell states with more than one measurement",
      "date": "2026-09-21",
      "journal": "Nature Aging",
      "authors": "Ke Zhang, Xingjian Chen, et al.",
      "doi": "10.1038/s43587-026-01219-7",
      "url": "https://www.nature.com/articles/s43587-026-01219-7",
      "countries": [
        "United States"
      ],
      "region": "United States",
      "model": "Animal tissue profiling",
      "kind": "Research paper",
      "outcome": "Measurement method",
      "topic": "Measurement",
      "image": 9,
      "access": "Publisher abstract and selected main-text sections checked. Figures and raw imaging datasets were not independently analyzed.",
      "sample": "Mouse skin, lung, and wound-repair models.",
      "finding": "The study combines Raman imaging with molecular profiling to examine senescence-associated states in aging and repair. Its multimodal design links spatial chemical information with cell-state measurements rather than depending on a single marker.",
      "limit": "An informative measurement platform is not a rejuvenation treatment. Tissue-specific signatures need independent validation before being treated as a general-purpose aging assay.",
      "question": "Can a multimodal measurement detect a meaningful functional change without merely detecting tissue composition?",
      "endpoint": "Spatial vibrational signatures, transcriptomic states, and senescence-associated tissue patterns."
    },
    {
      "id": "cell-painting",
      "title": "Deciphering senescence-associated mechanisms through cell painting & transcriptomics",
      "short": "Senescence is not one uniform cell state",
      "date": "2026-09-17",
      "journal": "npj Aging",
      "authors": "Yuliana Tan, Anika Liu, Emily Larkin, et al.",
      "doi": "10.1038/s41514-026-00500-8",
      "url": "https://www.nature.com/articles/s41514-026-00500-8",
      "countries": [
        "Germany"
      ],
      "region": "Europe",
      "model": "Human cells in culture",
      "kind": "Research paper",
      "outcome": "Measurement method",
      "topic": "Senescence",
      "image": 12,
      "access": "Publisher abstract, introductory material, and author disclosures checked. Full datasets not reanalyzed.",
      "sample": "Cultured human dermal and lung fibroblast models.",
      "finding": "Cell painting and transcriptomics helped distinguish senescence-associated states produced by different conditions, as well as quiescence and responses to senolytic exposure. The work argues for more than one way of measuring a heterogeneous state.",
      "limit": "The findings are from cultured cells, not patients. Classification performance within one experimental setting is not a universal diagnostic test. Company employment was disclosed by authors.",
      "question": "Which combinations of measurements distinguish useful repair states from persistently harmful cell states?",
      "endpoint": "Cell morphology, transcriptional patterns, and treatment-response profiles."
    },
    {
      "id": "plpp2-liver-repair",
      "title": "Phospholipid phosphatase 2 drives liver repair and regeneration after acute liver injury",
      "short": "Repair depends on the tissue’s metabolic context",
      "date": "2026-10-08",
      "journal": "Signal Transduction and Targeted Therapy",
      "authors": "Fan Li, Yiming Wang, et al.",
      "doi": "10.1038/s41392-026-02825-y",
      "url": "https://www.nature.com/articles/s41392-026-02825-y",
      "countries": [
        "China"
      ],
      "region": "China",
      "model": "Human observation + animals",
      "kind": "Research paper",
      "outcome": "Mechanistic finding",
      "topic": "Tissue repair",
      "image": 17,
      "access": "Publisher abstract and selected introductory text checked. Full methods not independently audited.",
      "sample": "Human injury-related observations and mouse liver-injury models.",
      "finding": "PLPP2 was investigated as a regulator of repair after acute liver injury, connecting phospholipid metabolism, cellular stress, and regeneration. The study combines human observations with causal experiments in mice.",
      "limit": "An injury-repair mechanism is not automatically an anti-aging intervention. The evidence does not establish an approved treatment or demonstrate whole-body rejuvenation.",
      "question": "Does the pathway support safe, durable recovery in aged tissue, and when would intervention be counterproductive?",
      "endpoint": "Acute liver injury, metabolic regulation, and regenerative response."
    },
    {
      "id": "er100-sponsor-update",
      "title": "Life Biosciences Announces First-in-Human Data from Ongoing Phase 1 Trial Evaluating ER-100 in Optic Neuropathies",
      "short": "An early human signal, reported by the sponsor",
      "date": "2026-10-08",
      "journal": "Life Biosciences — sponsor statement",
      "authors": "Life Biosciences",
      "doi": null,
      "url": "https://www.lifebiosciences.com/life-biosciences-announces-first-in-human-data-from-ongoing-phase-1-trial-evaluating-er-100-in-optic-neuropathies/",
      "countries": [
        "United States"
      ],
      "region": "United States",
      "model": "Early human study",
      "kind": "Sponsor update",
      "outcome": "Preliminary safety report",
      "topic": "Cell identity",
      "image": 4,
      "access": "Official sponsor statement checked. Not a peer-reviewed efficacy report.",
      "sample": "Three participants; sponsor-reported follow-up through day 56.",
      "finding": "The sponsor reported initial tolerability observations in three participants with glaucoma and preliminary visual-field changes in two. This is an early phase 1 update for a specific eye-disease program.",
      "limit": "Tiny, uncontrolled, sponsor-reported results cannot establish efficacy, general age reversal, or long-term safety. This update must not be counted as an independent replication of the underlying scientific approach.",
      "question": "What will prespecified controlled outcomes and longer safety follow-up show?",
      "endpoint": "Early safety observations and exploratory visual-function measures."
    },
    {
      "id": "gnptab-sting-senescence",
      "source_id": "C01",
      "source_number": 1,
      "short": "GNPTAB–STING: separate harmful signaling from maintenance",
      "title": "CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence. Protein & Cell. 27 July 2026.",
      "date": "2026-07-27",
      "region": "China",
      "countries": [
        "China"
      ],
      "model": "Human cell models",
      "domain": "Cellular aging",
      "method": "Cas9 screen",
      "target": "GNPTAB / STING",
      "species": "Human",
      "direction": "Disruption; overexpression; interaction separation",
      "cell": "Human mesenchymal progenitor cells",
      "delivery": "Cell-based perturbations",
      "finding": "A focused Cas9 screen identified GNPTAB as a regulator of senescence. The assessment describes a noncanonical interaction with STING and a binding-deficient mutant that retained the tested lysosomal functions without inducing senescence.",
      "limit": "This is mechanistic human-cell evidence, not treatment of people. Deleting or suppressing GNPTAB everywhere would not follow from an interaction-specific result.",
      "question": "Can the unwanted interaction be interrupted while preserving essential maintenance, and does the benefit replicate independently?",
      "endpoint": "Senescence-associated behavior; inflammatory signaling; tested lysosomal functions.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": "Preservation of tested canonical lysosomal functions was described; wider safety remains unresolved.",
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1093/procel/pwag049",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Cell identity",
      "image": 12,
      "journal": "Protein & Cell",
      "authors": "Yin J, Gao Y, Jing Y, et al",
      "doi": "10.1093/procel/pwag049"
    },
    {
      "id": "aged-t-cell-crispr",
      "source_id": "C02",
      "source_number": 2,
      "short": "Aged T-cell function: the intervention direction matters",
      "title": "CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer. Cell. 29 July 2026.",
      "date": "2026-07-29",
      "region": "United States",
      "countries": [
        "United States"
      ],
      "model": "Animals + human association",
      "domain": "Immune function",
      "method": "Cas9 screen",
      "target": "Dusp5 / Zfp219; human ZNF219",
      "species": "Mouse; human association",
      "direction": "Loss of function; combination with checkpoint inhibition",
      "cell": "T cells in an aged tumor environment",
      "delivery": "Experimental immune-cell perturbation",
      "finding": "Screens identified Dusp5 and Zfp219 as regulators of T-cell expansion or cytotoxic function. Zfp219 loss combined with checkpoint inhibition improved tumor control in aged mice; the human ZNF219 observations were associative.",
      "limit": "Mouse tumor control is not proof of general human immune rejuvenation. Dusp5, Zfp219 and human ZNF219 cannot be used interchangeably.",
      "question": "Which immune function changes, in which model, and can an independent specialist reproduce the result?",
      "endpoint": "T-cell expansion, cytotoxic function and mouse tumor control.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1016/j.cell.2026.07.016",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Senescence",
      "image": 12,
      "journal": "Cell",
      "authors": "Chen ACY, Ji KY, Yerinde C, et al",
      "doi": "10.1016/j.cell.2026.07.016"
    },
    {
      "id": "compact-cas12m",
      "source_id": "C04",
      "source_number": 4,
      "short": "Compact Cas12m is an enabling technology, not an aging treatment",
      "title": "Structure-guided discovery and engineering of miniature CRISPR–Cas12m for epigenome editing. Nature Structural & Molecular Biology. 16 September 2026.",
      "date": "2026-09-16",
      "region": "China",
      "countries": [
        "China"
      ],
      "model": "Cells + animals",
      "domain": "Editing technology",
      "method": "Epigenome editing",
      "target": "xCas12m / experimental silencing targets",
      "species": "Human cells; mouse disease model",
      "direction": "Gene regulation / silencing",
      "cell": "Human-cell experiments; mouse hepatitis B model",
      "delivery": "AAV delivery in the reported mouse application",
      "finding": "Structure-guided engineering produced a compact DNA-binding system and epigenetic regulation in human cells, with a silencing application in a mouse hepatitis B model. The central contribution is regulator size and control.",
      "limit": "The system is Cas12m, not Cas9. A successful viral-disease model does not establish delivery or rejuvenation in aged muscle, brain or other tissues.",
      "question": "Does compactness solve a real delivery constraint after a biological target and tissue have been selected?",
      "endpoint": "Gene regulation and silencing in the reported cell and disease-model settings.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41594-026-01890-9",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Structural & Molecular Biology",
      "authors": "Yu T, Ji M, Yu D, et al",
      "doi": "10.1038/s41594-026-01890-9"
    },
    {
      "id": "optiprime",
      "source_id": "C05",
      "source_number": 5,
      "short": "OptiPrime: prediction with an explicit validation boundary",
      "title": "Mechanistic machine learning for prediction of prime editing outcomes. Nature Biotechnology. 12 August 2026.",
      "date": "2026-08-12",
      "region": "Not assigned",
      "countries": [],
      "model": "Computational + cells",
      "domain": "Editing technology",
      "method": "Prime editing prediction",
      "target": "Design-specific prime-editing targets",
      "species": "Multiple experimental systems",
      "direction": "Prediction / candidate ranking",
      "cell": "Several disease-relevant settings, including primary cells",
      "delivery": "Setting-specific; no universal organ delivery claim",
      "finding": "OptiPrime combines mechanistic modeling with machine learning to rank prime-editing strategies. The assessment reports prospective evaluation in disease-relevant settings, including primary cells.",
      "limit": "Predicted performance is not a safety certification. Commercial reuse requires a separate rights assessment; the publisher states that the code and server are for noncommercial use.",
      "question": "Does the model improve a defined decision on an appropriate held-out dataset, under permitted use?",
      "endpoint": "Prime-editing outcome prediction compared with measured experimental outcomes.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": "Publisher data and code statements provide access routes; Karam has not imported or validated these datasets.",
      "url": "https://doi.org/10.1038/s41587-026-03261-7",
      "access": "Publisher code-availability statement checked on 15 October 2026. It describes OptiPrime code and hosted service as noncommercial-use only.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Biotechnology",
      "authors": "Hsu A, Chen PJ, Li AH, et al",
      "doi": "10.1038/s41587-026-03261-7"
    },
    {
      "id": "organ-specific-editing-outcomes",
      "source_id": "C06",
      "source_number": 6,
      "short": "Off-target findings differ across cells and organs",
      "title": "Single-cell and in vivo profiling reveal heterogeneous and organ-specific CRISPR-Cas9 off-target and translocation outcomes. Nature Communications. 26 August 2026;17:9067.",
      "date": "2026-08-26",
      "region": "Not assigned",
      "countries": [],
      "model": "Cells + animals",
      "domain": "Editing technology",
      "method": "Cas9 outcome profiling",
      "target": "Guide- and tissue-specific loci",
      "species": "Cells and mice",
      "direction": "Off-target / translocation measurement",
      "cell": "Individual cells and mouse tissues",
      "delivery": "Experimental cell- and organ-specific contexts",
      "finding": "Single-cell and in vivo profiling found heterogeneous off-target and translocation outcomes, including events obscured by bulk analysis. Some experiments deliberately used a promiscuous guide.",
      "limit": "The work does not provide a universal error rate for every editor or clinical guide. Results depend on the guide, cell population, delivery and assay sensitivity.",
      "question": "What events might the selected measurement strategy miss in the actual tissue and cell population of interest?",
      "endpoint": "Off-target edits and translocation profiles by cell and organ.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": "Study subject: unintended sequence changes and rearrangements; not a complete product safety certification.",
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41467-026-77144-5",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Communications",
      "authors": "Madsen A, Selfjord N, Martinez-Lage M, et al",
      "doi": "10.1038/s41467-026-77144-5"
    },
    {
      "id": "crisprlungo",
      "source_id": "C07",
      "source_number": 7,
      "short": "CRISPRLungo: read more than an editing percentage",
      "title": "Analysing long-read CRISPR experiments with CRISPRLungo. Nature Biomedical Engineering. 20 August 2026.",
      "date": "2026-08-20",
      "region": "Not assigned",
      "countries": [],
      "model": "Computational + experimental data",
      "domain": "Editing technology",
      "method": "Long-read outcome analysis",
      "target": "Edited alleles and structural outcomes",
      "species": "Edited samples; assay-dependent",
      "direction": "Measurement / allele classification",
      "cell": "Long-read amplicon sequencing datasets",
      "delivery": "Not a delivery platform",
      "finding": "CRISPRLungo analyzes long-read amplicon data to distinguish edited alleles and structural outcomes such as larger deletions and inversions. The author-lab description includes error correction, statistical filtering and a browser application.",
      "limit": "A targeted amplicon assay does not establish that the whole genome is free of unintended changes. Karam has not independently validated this pipeline or adopted it as a commercial service.",
      "question": "Which outcome classes, controls, assay blind spots and software version should be required before interpreting a dataset?",
      "endpoint": "Allele classification, small sequence changes and structural outcomes within the assayed region.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": "Author repository and browser application linked in the analysis directory.",
      "url": "https://doi.org/10.1038/s41551-026-01776-7",
      "access": "Author-laboratory publication abstract, repository and browser-tool page located on 15 October 2026; no independent software performance test.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Biomedical Engineering",
      "authors": "Hwang GH, Vyshedskiy B, Barry T, et al",
      "doi": "10.1038/s41551-026-01776-7"
    },
    {
      "id": "primary-myeloid-screening",
      "source_id": "C08",
      "source_number": 8,
      "short": "Primary myeloid screens reveal context-specific inflammatory effects",
      "title": "Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells. Nature Biotechnology. 17 August 2026.",
      "date": "2026-08-17",
      "region": "Not assigned",
      "countries": [],
      "model": "Primary human cells",
      "domain": "Immune function",
      "method": "Cas9 screen",
      "target": "TNFAIP3 and other regulators",
      "species": "Human",
      "direction": "Disruption; context-dependent inflammation",
      "cell": "Monocytes, macrophages and dendritic cells",
      "delivery": "Virus-like particles",
      "finding": "Virus-like particle tools enabled targeted engineering and pooled screening of primary human myeloid cells. In the macrophage context highlighted in the assessment, disrupting TNFAIP3 promoted inflammation.",
      "limit": "A gene name is not an intervention recommendation. An effect can have the opposite direction from what another cell type or disease context might suggest.",
      "question": "Can a partner connect a defined perturbation to specialized immune function rather than generic proliferation?",
      "endpoint": "Editing feasibility and regulators of inflammatory polarization.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41587-026-03258-2",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Senescence",
      "image": 12,
      "journal": "Nature Biotechnology",
      "authors": "Jung H, Devant P, Ching C, et al",
      "doi": "10.1038/s41587-026-03258-2"
    },
    {
      "id": "prime-assembly-integration",
      "source_id": "C09",
      "source_number": 9,
      "short": "Prime assembly: large DNA changes remain context-specific",
      "title": "Precise genomic integration of large DNA fragments by donor-directed annealing using prime editing. Nature Biotechnology. 28 August 2026.",
      "date": "2026-08-28",
      "region": "South Korea",
      "countries": [
        "South Korea"
      ],
      "model": "Cells + animals",
      "domain": "Editing technology",
      "method": "Prime editing",
      "target": "Targeted integration sites",
      "species": "Human cells; experimental mouse context",
      "direction": "Targeted integration / replacement",
      "cell": "Primary human T cells and additional experimental systems",
      "delivery": "Different delivery settings reported",
      "finding": "The assessment describes donor-directed annealing with prime editing for large genomic replacement. One reported application was targeted CAR insertion into primary human T cells, with efficiency up to 28.1%.",
      "limit": "Cell-line maxima, primary-cell results and mouse delivery are different experiments. They cannot be combined into one general performance promise or a claim of age reversal.",
      "question": "What is the useful output in the exact target cell type, and which unintended integration outcomes require measurement?",
      "endpoint": "Large-fragment integration, replacement and context-specific editing efficiency.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41587-026-03301-2",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Biotechnology",
      "authors": "Jung H, Jeong B, Kim YW, et al",
      "doi": "10.1038/s41587-026-03301-2"
    },
    {
      "id": "abasic-guide-specificity",
      "source_id": "C10",
      "source_number": 10,
      "short": "Guide chemistry can change specificity",
      "title": "Abasic CRISPR RNAs inherently harness fidelity of SpCas9 for genome editing. Nature Chemical Biology. 5 February 2026.",
      "date": "2026-02-05",
      "region": "South Korea",
      "countries": [
        "South Korea"
      ],
      "model": "Experimental cells",
      "domain": "Editing technology",
      "method": "Guide chemistry",
      "target": "SpCas9 guide / experimental loci",
      "species": "Experimental systems",
      "direction": "Guide modification",
      "cell": "Experimental cells; wider tissue performance not established",
      "delivery": "Guide-RNA modification",
      "finding": "Abasic modifications inspired by bacterial CRISPR RNAs reduced off-target cleavage while retaining useful on-target activity in the reported experimental systems.",
      "limit": "Reduced off-target activity is not zero off-target activity, and this is not general human safety evidence. The paper is earlier-2026 context, not a last-three-months finding.",
      "question": "What comparison would establish useful guide performance in a chosen model without converting a specificity signal into a guarantee?",
      "endpoint": "On-target and off-target cleavage in the evaluated systems.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41589-026-02139-8",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Chemical Biology",
      "authors": "Gu D, Kim GWD, Park M, et al",
      "doi": "10.1038/s41589-026-02139-8"
    },
    {
      "id": "top2b-senescence",
      "source_id": "C11",
      "source_number": 11,
      "short": "An edit can worsen senescence: TOP2B in HEK293T cells",
      "title": "Deletion of TOP2B promoter using CRISPR-Cas9 induces senescence in HEK 293T cells. Biochemistry and Biophysics Reports. 19 May 2026;46:102620.",
      "date": "2026-05-19",
      "region": "India",
      "countries": [
        "India"
      ],
      "model": "Immortalized cell line",
      "domain": "Cellular aging",
      "method": "Cas9 nuclease",
      "target": "TOP2B promoter",
      "species": "Human-derived immortalized line",
      "direction": "Promoter deletion",
      "cell": "HEK293T cells",
      "delivery": "Laboratory Cas9 perturbation",
      "finding": "Researchers at the University of Hyderabad disrupted the TOP2B promoter in HEK293T cells and observed senescence. It is a useful counterexample to the idea that removing gene activity necessarily rejuvenates cells.",
      "limit": "HEK293T is an immortalized laboratory model, not normal aged human tissue. The finding is a directional warning, not a validated human-aging target.",
      "question": "Is a candidate intervention impairing cell maintenance rather than restoring it, and does the chosen model expose that risk?",
      "endpoint": "Senescent phenotypes following promoter disruption.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1016/j.bbrep.2026.102620",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Adverse cellular effect",
      "topic": "Cell identity",
      "image": 12,
      "journal": "Biochemistry and Biophysics Reports",
      "authors": "Saroj N, Velangani HG, Kiran S, Dholaniya PS",
      "doi": "10.1016/j.bbrep.2026.102620"
    },
    {
      "id": "polr2a-crispra",
      "source_id": "C12",
      "source_number": 12,
      "short": "POLR2A activation: cellular findings are not a checkpoint bypass license",
      "title": "LMO7-mediated POLR2A degradation promotes cellular senescence through the MDM4/p53/p21 axis. Cell Death & Disease. 28 March 2026;17:421.",
      "date": "2026-03-28",
      "region": "China",
      "countries": [
        "China"
      ],
      "model": "Cellular experiment",
      "domain": "Cellular aging",
      "method": "CRISPRa",
      "target": "LMO7 / POLR2A / MDM4-p53-p21",
      "species": "Cellular system",
      "direction": "Activation",
      "cell": "Senescence-associated cellular model",
      "delivery": "Endogenous gene activation",
      "finding": "Activating endogenous POLR2A with CRISPRa alleviated senescent phenotypes in the reported system. The assessment describes a pathway connecting LMO7-mediated regulation with MDM4, p53 and p21.",
      "limit": "This does not show that broad suppression of protective p53 signaling is a healthy-aging strategy. Specific context, identity and growth safeguards must remain visible.",
      "question": "Can function improve without merely permitting damaged cells to escape growth arrest?",
      "endpoint": "Cellular senescence-associated phenotypes and pathway relationships.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41419-026-08679-0",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Cell identity",
      "image": 12,
      "journal": "Cell Death & Disease",
      "authors": "Lai C, Fu W, Liu J, et al",
      "doi": "10.1038/s41419-026-08679-0"
    },
    {
      "id": "mitoperturb-seq",
      "source_id": "C13",
      "source_number": 13,
      "short": "MitoPerturb-Seq: nuclear regulation of mitochondrial outcomes",
      "title": "MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy. Nature Structural & Molecular Biology. 1 April 2026;33:711–723.",
      "date": "2026-04-01",
      "region": "United Kingdom",
      "countries": [
        "United Kingdom"
      ],
      "model": "Single-cell perturbation study",
      "domain": "Cellular aging",
      "method": "CRISPR screening / single-cell readout",
      "target": "Nuclear regulators of mitochondrial DNA",
      "species": "Cell systems",
      "direction": "Gene-specific perturbation",
      "cell": "Single-cell mitochondrial-response models",
      "delivery": "Nuclear perturbation; not ordinary direct mitochondrial Cas9 editing",
      "finding": "MitoPerturb-Seq interrogates nuclear genes involved in mitochondrial DNA copy number and heteroplasmy at single-cell resolution. The measured response links nuclear perturbations with mitochondrial state.",
      "limit": "The method should not be described as routine direct mitochondrial DNA editing with ordinary Cas9 and a standard guide. Human therapeutic benefit is not established.",
      "question": "Which mitochondrial functional outcome matters beyond copy number, and how should nuclear and mitochondrial interventions be distinguished?",
      "endpoint": "Mitochondrial DNA depletion, copy number and heteroplasmy responses.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41594-026-01779-7",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Cell identity",
      "image": 12,
      "journal": "Nature Structural & Molecular Biology",
      "authors": "Burr SP, Auckland K, Glynos A, et al",
      "doi": "10.1038/s41594-026-01779-7"
    },
    {
      "id": "lnp-prime-editing",
      "source_id": "C14",
      "source_number": 14,
      "short": "Nonviral prime editing: a delivery result in mouse liver",
      "title": "Efficient prime editing in vivo and in vitro using lipid nanoparticles. Nature Nanotechnology. 15 June 2026;21:1022–1035.",
      "date": "2026-06-15",
      "region": "United States",
      "countries": [
        "United States"
      ],
      "model": "Cells + animals",
      "domain": "Editing technology",
      "method": "Prime editing",
      "target": "Disease-specific sequence targets",
      "species": "Cells and mice",
      "direction": "Sequence correction",
      "cell": "Mouse liver, including a phenylketonuria model",
      "delivery": "Lipid nanoparticles",
      "finding": "The assessment reports improved prime editing using lipid nanoparticles, including correction in a mouse phenylketonuria model. Delivery and RNA cargo design materially affected outcomes.",
      "limit": "Performance in mouse liver is not a demonstration of delivery to every organ, and does not establish treatment of normal aging in people.",
      "question": "Does the proposed target have a compatible sequence change, a plausible tissue route and an independent measure of benefit?",
      "endpoint": "Prime-editing efficiency and disease-model correction.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41565-026-02200-6",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "Nature Nanotechnology",
      "authors": "Jiang AY, Cristian A, Brooks DL, et al",
      "doi": "10.1038/s41565-026-02200-6"
    },
    {
      "id": "ctx310-durability",
      "source_id": "C15",
      "source_number": 15,
      "short": "CTX310: durable lipid biomarkers are not lifespan evidence",
      "title": "Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310. New England Journal of Medicine. Online 28 August 2026;395:1343–1345.",
      "date": "2026-08-28",
      "region": "Not assigned",
      "countries": [],
      "model": "Early human intervention",
      "domain": "Clinical context",
      "method": "In vivo CRISPR-Cas9",
      "target": "ANGPTL3",
      "species": "Human",
      "direction": "Disease-related target editing",
      "cell": "Participants in an early-phase cardiovascular-risk program",
      "delivery": "Product-specific in vivo editing",
      "finding": "A phase 1a report described one-year durability of ANGPTL3 and lipid reductions after CTX310. The assessment notes that the abstract reported no treatment-related dose-limiting toxic effects.",
      "limit": "Biomarker reductions do not establish fewer cardiovascular events or longer life. A small early-phase safety report is not a guarantee of long-term product safety.",
      "question": "Which patient-relevant clinical outcomes remain untested, and what longer follow-up is required?",
      "endpoint": "ANGPTL3 and lipid biomarkers; early safety observations.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": "One-year durability as summarized in the assessment.",
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1056/NEJMc2609825",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Targeted delivery",
      "image": 12,
      "journal": "New England Journal of Medicine",
      "authors": "Laffin LJ, Nicholls SJ, Scott RS",
      "doi": "10.1056/NEJMc2609825"
    },
    {
      "id": "methanotroph-crispri",
      "source_id": "C22",
      "source_number": 22,
      "short": "Methanotroph screening: growth is not net climate benefit",
      "title": "CRISPRi-based functional genomic screening identifies genes essential for CH4-dependent growth in a methanotrophic bacterium. Science Advances. 24 April 2026;12:eaed4234.",
      "date": "2026-04-24",
      "region": "United States",
      "countries": [
        "United States"
      ],
      "model": "Contained microbial experiment",
      "domain": "Climate biology",
      "method": "CRISPRi screen",
      "target": "Methane-dependent growth regulators",
      "species": "Methylococcus capsulatus",
      "direction": "Gene repression screen",
      "cell": "Methane-consuming bacterial culture",
      "delivery": "Contained laboratory setting",
      "finding": "A CRISPRi screen of approximately 45,000 guides identified determinants of methane-dependent growth and informed improved culture productivity.",
      "limit": "The study does not demonstrate low-cost industrial treatment of ambient atmospheric methane or a net greenhouse-gas benefit. Productivity, methane removal and life-cycle impact are different outcomes.",
      "question": "At a defined emissions source, would a contained process outperform existing treatment and an unmodified biological baseline?",
      "endpoint": "Methane-dependent growth and laboratory culture productivity.",
      "donor_context": null,
      "comparator": null,
      "sample": "Approximately 45,000 guides; guide count is not an independent biological sample size.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1126/sciadv.aed4234",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Science Advances",
      "authors": "Henard JM, Lee SA, Yu YC, Shao D, Azad RK, Henard CA",
      "doi": "10.1126/sciadv.aed4234"
    },
    {
      "id": "sorghum-regulatory-map",
      "source_id": "C23",
      "source_number": 23,
      "short": "Sorghum regulatory maps: expression is not carbon removal",
      "title": "Mapping cis-regulatory mutations at scale in sorghum enables modulation of gene expression. Nature Biotechnology. 27 March 2026.",
      "date": "2026-03-27",
      "region": "Not assigned",
      "countries": [],
      "model": "Plant reporter assays",
      "domain": "Climate biology",
      "method": "CRISPR-accessible regulatory mapping",
      "target": "Photosynthesis-related cis-regulatory sites",
      "species": "Sorghum",
      "direction": "Regulatory variation / expression modulation",
      "cell": "Plant reporter-assay context",
      "delivery": "Assay-based regulatory mapping",
      "finding": "A sorghum regulatory map measured more than 30,000 CRISPR-accessible mutations in reporter assays. The output highlighted in the assessment was changed expression of photosynthesis-related proteins.",
      "limit": "A percentage change in protein expression is not the same percentage change in crop yield or carbon removal. Carbon-storage durability was not established by this readout.",
      "question": "How would a regulatory finding translate into field performance and a separate durable-storage claim?",
      "endpoint": "Reporter and photosynthesis-related protein expression.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41587-026-03046-y",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Nature Biotechnology",
      "authors": "Groover ED, Ding D, Wang FZ, et al",
      "doi": "10.1038/s41587-026-03046-y"
    },
    {
      "id": "rice-methane-transgenic",
      "source_id": "C24",
      "source_number": 24,
      "short": "Rice methane reductions: useful biology, not a CRISPR result",
      "title": "Reduced methane emissions in transgenic rice genotypes are associated with altered rhizosphere microbial hydrogen cycling. Nature Communications. 26 January 2026;17:2028.",
      "date": "2026-01-26",
      "region": "Not assigned",
      "countries": [],
      "model": "Greenhouse plant experiment",
      "domain": "Climate biology",
      "method": "Transgenic overexpression — not CRISPR",
      "target": "Rhizosphere hydrogen-cycling relationships",
      "species": "Rice and associated microbes",
      "direction": "Overexpression",
      "cell": "Two transgenic rice genotypes in greenhouse conditions",
      "delivery": "Plant genetic engineering, not the CRISPR intervention category",
      "finding": "The assessment reports 38% and 58% lower cumulative methane over 70 days for two transgenic rice genotypes. One genotype also showed adverse seed-production traits.",
      "limit": "This used overexpression rather than CRISPR. Greenhouse emissions reductions do not establish field-scale agronomic performance or a commercially useful net climate outcome.",
      "question": "Do any emissions gains persist alongside yield, seed production and other greenhouse-gas trade-offs?",
      "endpoint": "Cumulative methane and seed-production traits.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": "70 days in the reported greenhouse comparison.",
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41467-026-68640-9",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Nature Communications",
      "authors": "Shi LD, Ercoli MF, Kim J, et al",
      "doi": "10.1038/s41467-026-68640-9"
    },
    {
      "id": "wlg-rice-resilience",
      "source_id": "C25",
      "source_number": 25,
      "short": "WLG rice resilience: adaptation is its own outcome",
      "title": "WLG coordinates multi-stress tolerance in rice by regulating DST-dependent H2O2 homeostasis and stomatal aperture. Nature Communications. 16 September 2026.",
      "date": "2026-09-16",
      "region": "China",
      "countries": [
        "China"
      ],
      "model": "Plant mechanistic study",
      "domain": "Climate biology",
      "method": "Regulatory mechanism study",
      "target": "WLG / DST / Prx24",
      "species": "Rice",
      "direction": "Regulation of stress responses",
      "cell": "Drought, salt and heat stress contexts",
      "delivery": "Plant experimental setting",
      "finding": "The WLG–DST–Prx24 regulatory module was associated with multi-stress tolerance, plant water retention and stress responses in rice.",
      "limit": "This is adaptation research. It does not measure global temperature reduction, methane mitigation or permanent carbon storage.",
      "question": "Which stress, crop-performance endpoint and operating conditions define a useful adaptation result?",
      "endpoint": "Water retention and responses to drought, salt and heat.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41467-026-77791-8",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Nature Communications",
      "authors": "Wang Z, Wang S, Yue Z, et al",
      "doi": "10.1038/s41467-026-77791-8"
    },
    {
      "id": "osrlk-root-microbiome",
      "source_id": "C26",
      "source_number": 26,
      "short": "OsRLK: distinguish mechanism tests from the beneficial field intervention",
      "title": "Wild rice locus enables microbiome re-domestication for enhanced nitrogen-use efficiency. Nature Microbiology. 30 September 2026.",
      "date": "2026-09-30",
      "region": "China",
      "countries": [
        "China"
      ],
      "model": "Plants + field trials",
      "domain": "Climate biology",
      "method": "Cas9 validation + overexpression",
      "target": "OsRLK",
      "species": "Rice and root-associated microbes",
      "direction": "Knockout for mechanism; overexpression for beneficial traits",
      "cell": "Root microbiome and nitrogen-use context",
      "delivery": "Separate plant validation and field comparisons",
      "finding": "Cas9 knockout lines helped validate a mechanism linking OsRLK with root-associated microbes and nitrogen-use efficiency. The beneficial yield-related field results came from overexpression lines.",
      "limit": "Calling the favorable field result a successful knockout would reverse the intervention. Better nutrient use alone does not quantify avoided nitrous oxide emissions.",
      "question": "Can mechanism, intervention direction, crop output and environmental accounting be kept separate in a development decision?",
      "endpoint": "Microbiome relationships, nitrogen use and field yield-related traits.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41564-026-02498-x",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Nature Microbiology",
      "authors": "Chang J, Wang D, Yao Z, et al",
      "doi": "10.1038/s41564-026-02498-x"
    },
    {
      "id": "rubisco-tale-editing",
      "source_id": "C27",
      "source_number": 27,
      "short": "Rubisco editing: TALE-based, not guide-RNA-directed CRISPR",
      "title": "Chloroplast genome editing of Rubisco boosts photosynthesis and plant growth. Nature Communications. 19 June 2026;17:5066.",
      "date": "2026-06-19",
      "region": "Japan",
      "countries": [
        "Japan"
      ],
      "model": "Plant experimental study",
      "domain": "Climate biology",
      "method": "TALE base editing — not CRISPR",
      "target": "Chloroplast Rubisco",
      "species": "Arabidopsis",
      "direction": "Chloroplast sequence editing",
      "cell": "Photosynthesis and plant-growth models",
      "delivery": "ptpTALECD chloroplast base editor",
      "finding": "A TALE-based chloroplast editor improved photosynthetic performance and plant growth in Arabidopsis. Its targeting system is not a guide-RNA-directed CRISPR platform.",
      "limit": "Faster plant growth is not evidence of durable atmospheric carbon removal. The molecular modality should not be mislabeled simply because both approaches edit genomes.",
      "question": "Which technology actually produced the result, and what additional storage and life-cycle evidence would a climate claim need?",
      "endpoint": "Photosynthetic performance and plant growth.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41467-026-73783-w",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Climate biology",
      "image": 12,
      "journal": "Nature Communications",
      "authors": "Yamori W, Nakazato I, Qu Y, et al",
      "doi": "10.1038/s41467-026-73783-w"
    },
    {
      "id": "self-limiting-drive",
      "source_id": "C31",
      "source_number": 31,
      "short": "Self-limiting mosquito drive: cage evidence, not field validation",
      "title": "Self-limiting population suppression gene drive design in the West Nile vector mosquito, Culex quinquefasciatus. Nature Communications. First published 26 May 2026;17:6847.",
      "date": "2026-05-26",
      "region": "Not assigned",
      "countries": [],
      "model": "Cage experiments + modeling",
      "domain": "Governance",
      "method": "Population gene drive",
      "target": "Inheritance system; no design details provided here",
      "species": "Culex quinquefasciatus",
      "direction": "Temporary population suppression",
      "cell": "Controlled mosquito cage populations",
      "delivery": "Contained proof of principle",
      "finding": "The assessment describes a self-limiting gene-drive proof of principle with temporary mosquito population suppression in cages, supported by modeling.",
      "limit": "Cage behavior does not establish reduced human disease, safe environmental release or a deployable climate product. No construction or release guidance is provided on this site.",
      "question": "What independent ecological, governance and disease-outcome evidence would be needed before a population intervention could even be considered?",
      "endpoint": "Temporary suppression in contained populations.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41467-026-73641-9",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Population models",
      "image": 12,
      "journal": "Nature Communications",
      "authors": "Feng X, Ding J, Liu Y, et al",
      "doi": "10.1038/s41467-026-73641-9"
    },
    {
      "id": "seed-bank-drive-model",
      "source_id": "C32",
      "source_number": 32,
      "short": "Dormant seeds change modeled gene-drive dynamics",
      "title": "Seed dormancy shapes gene drive dynamics in plants. Nature Plants. 3 April 2026;12:735–749. Modeling study.",
      "date": "2026-04-03",
      "region": "Not assigned",
      "countries": [],
      "model": "Modeling",
      "domain": "Governance",
      "method": "Population dynamics model",
      "target": "Seed dormancy and inheritance",
      "species": "Plants; modeled populations",
      "direction": "Model parameter comparison",
      "cell": "Dormant seed-bank scenarios",
      "delivery": "No field deployment",
      "finding": "A modeling study examined how dormant seed banks can delay spread and change predicted outcomes for plant gene drives.",
      "limit": "The work is modeling, not a field result or demonstrated climate intervention. A simple inheritance expectation does not determine ecosystem-scale behavior.",
      "question": "Which ecological assumptions dominate a proposed outcome, and how would model uncertainty be recorded?",
      "endpoint": "Predicted population trajectories under seed-dormancy assumptions.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41477-026-02256-1",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Population models",
      "image": 12,
      "journal": "Nature Plants",
      "authors": "Kim IK, Tian L, Chaffee R, et al",
      "doi": "10.1038/s41477-026-02256-1"
    },
    {
      "id": "malaria-climate-model",
      "source_id": "C35",
      "source_number": 35,
      "short": "Climate and malaria: a modeled health-resilience problem",
      "title": "Projected impacts of climate change on malaria in Africa. Nature. 28 January 2026;651:390–396. Modeling study.",
      "date": "2026-01-28",
      "region": "Not assigned",
      "countries": [],
      "model": "Modeling",
      "domain": "Governance",
      "method": "Climate-disease modeling",
      "target": "Malaria burden under climate scenarios",
      "species": "Human populations; vector-borne disease model",
      "direction": "Scenario comparison",
      "cell": "Africa under a specified climate scenario and control assumptions",
      "delivery": "Not an intervention or gene-drive trial",
      "finding": "The study projected increased malaria burden under specified climate and present-control assumptions, with disruption from extreme weather contributing to the modeled burden.",
      "limit": "A projection is not evidence that a gene drive works. Disease resilience is also not greenhouse-gas removal or planetary cooling.",
      "question": "Which scenario assumptions, control disruptions and public-health outcomes matter when comparing possible interventions?",
      "endpoint": "Projected malaria burden and contributions from extreme-weather disruption.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1038/s41586-025-10015-z",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Population models",
      "image": 12,
      "journal": "Nature",
      "authors": "Symons TL, Moran A, Balzarolo A, et al",
      "doi": "10.1038/s41586-025-10015-z"
    },
    {
      "id": "horizontal-transfer-model",
      "source_id": "C36",
      "source_number": 36,
      "short": "Horizontal gene transfer: an ecosystem model, not a deployed gene drive",
      "title": "Synthetic horizontal gene transfer for ecosystem restoration. Biology Direct. 14 August 2026. Accepted article; theoretical modeling.",
      "date": "2026-08-14",
      "region": "Not assigned",
      "countries": [],
      "model": "Theoretical modeling",
      "domain": "Governance",
      "method": "Synthetic horizontal transfer model",
      "target": "Microbial community properties",
      "species": "Modeled microbial communities",
      "direction": "Horizontal transfer / ecosystem model",
      "cell": "Theoretical restoration and dryland water-retention scenarios",
      "delivery": "No field deployment",
      "finding": "The assessment describes theoretical work on synthetic horizontal gene transfer in microbial communities, including possible dryland water-retention benefits.",
      "limit": "Horizontal transfer differs from biased parent-to-offspring inheritance. The paper is not evidence of a Cas9 climate product, safe field deployment or durable carbon removal.",
      "question": "What would distinguish a model prediction from an independently measured ecosystem benefit?",
      "endpoint": "Theoretical ecosystem behavior under specified transfer assumptions.",
      "donor_context": null,
      "comparator": null,
      "sample": "Not extracted in the supplied assessment.",
      "followup": null,
      "safety": null,
      "independent_replication": "Not established in the supplied assessment",
      "available_data": null,
      "url": "https://doi.org/10.1186/s13062-026-00919-9",
      "access": "Cited in the supplied 15 October 2026 project assessment; not independently reviewed in this website release.",
      "provenance": "External result summarized in CRISPR Project Assessment, 15 October 2026",
      "collection": "crispr",
      "kind": "Research paper",
      "outcome": "Context-specific evidence",
      "topic": "Population models",
      "image": 12,
      "journal": "Biology Direct",
      "authors": "Maull V, Aguadé-Gorgorió G, de Lorenzo V, Solé R",
      "doi": "10.1186/s13062-026-00919-9"
    }
  ],
  "collections": {
    "core": 15,
    "crispr": 26,
    "shared": 2,
    "unique_records": 39
  }
}