{"schemaVersion":"maha-epistemic/1.0","evidencePolicyVersion":"mps/0.1","recordId":"urn:maha:record:in-vivo-genome-editing-workflow","canonicalPath":"/knowledge/synthetic-biology/methods/in-vivo-genome-editing-workflow","contentHash":"sha256:be7269de29ceb69f04304eac58a054460ee0d667332fa5cde126210fbffb52f9","generatedAt":"2026-08-30T16:02:47.346Z","publicationDecision":{"recordId":"urn:maha:record:in-vivo-genome-editing-workflow","publicEligible":true,"evaluatedAgainst":"maha-epistemic/1.0","reasons":[]},"claims":[{"id":"urn:maha:claim:in-vivo-genome-editing-workflow","scope":"The constructs, biological systems, protocols, assays, datasets, and comparisons reported in CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis.","boundary":"Early dose-cohort observations do not establish long-term benefit, rare-event safety, repeatability, or transfer to another organ and target.","claimKind":"empirical-claim","sourceIds":["source-gillmore-in-vivo-2021"],"statement":"The cited phase 1 report describes systemic administration, dose cohorts, biomarker response, and early safety observations for a liver-targeted CRISPR intervention.","replication":{"asOfDate":"2026-08-24","assessment":"This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded.","independentReplicationCount":null},"uncertainty":{"kind":"qualitative","statement":"There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices."},"evidenceMaturity":"single-study"}],"sources":[{"id":"source-gillmore-in-vivo-2021","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107454","title":"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis","rights":{"note":"Maha paraphrases the source-level result and links to the version of record; no article passage is reproduced.","basis":"citation-with-paraphrase","quotationUsed":false},"authors":["Julian D. Gillmore","Ed Gane","Julian Taubel","Jingzhu Kao","et al."],"boundary":"Early biomarker and safety observations do not establish long-term clinical benefit, rare-event safety, or transfer to other tissues and targets.","publisher":"The New England Journal of Medicine","establishes":"The phase 1 report describes systemic lipid-nanoparticle delivery of CRISPR components and early dose-cohort biomarker and safety observations in adults with transthyretin amyloidosis.","identifiers":[{"value":"10.1056/NEJMoa2107454","scheme":"doi"}],"publishedAt":"2021-06-26","exactLocator":"Abstract; Methods; Results; Figures 1–3; supplementary protocol and statistical analysis.","conflictsOfInterest":"The study was funded by Intellia Therapeutics and Regeneron Pharmaceuticals; author relationships are disclosed."}],"reviewEvents":[{"scope":"source-fidelity","verdict":"approve","reviewId":"epireview_9f29035a69144d16adfb4f0928d59e26","rationale":"In-vivo genome-editing workflow binds claim urn:maha:claim:in-vivo-genome-editing-workflow only to CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis at NEJM DOI 10.1056/NEJMoa2107454, Abstract; Clinical Study Treatment; Assessments. The audit inspected version-of-record at declared inspected location depth and recorded subject and claim support; the claim remains limited to “The constructs, biological systems, protocols, assays, datasets, and comparisons reported in CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis.”. This decision applies only to record urn:maha:record:in-vivo-genome-editing-workflow at sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.349Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"domain-fidelity","verdict":"approve","reviewId":"epireview_7b56c8fad42941dc9fca7ad7b2039511","rationale":"In-vivo genome-editing workflow remains within domain synthetic-biology. Its mechanism or method is the bounded proposition “The cited phase 1 report describes systemic administration, dose cohorts, biomarker response, and early safety observations for a liver-targeted CRISPR intervention.”; the record does not transfer that proposition beyond Early dose-cohort observations do not establish long-term benefit, rare-event safety, repeatability, or transfer to another organ and target. This decision applies only to record urn:maha:record:in-vivo-genome-editing-workflow at sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.416Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"boundary-adequacy","verdict":"approve","reviewId":"epireview_5c816d25de82477e96c29d7b7b25b302","rationale":"In-vivo genome-editing workflow retains uncertainty “There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices.” and replication assessment “This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded.”. Its non-claims and 2 prohibited inference(s) remain attached to every reuse. This decision applies only to record urn:maha:record:in-vivo-genome-editing-workflow at sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.482Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"rights-and-locator","verdict":"approve","reviewId":"epireview_601eb94d58054e4bb70fb6ce687e5543","rationale":"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis is identified by doi:10.1056/NEJMoa2107454, inspected at Abstract; Methods; Results; Figures 1–3; supplementary protocol and statistical analysis., and retained under citation-with-paraphrase. This approval binds only exact revision sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6. This decision applies only to record urn:maha:record:in-vivo-genome-editing-workflow at sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.564Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:c04affa4a87aba09a28285d08ee2c933963509ae9064cedf1a66c4dff7cd4dd6","supersedesReviewId":null,"reviewerProfileVersion":1}]}