{"schemaVersion":"maha-epistemic/1.0","evidencePolicyVersion":"mps/0.1","recordId":"urn:maha:record:guide-rna-and-pam-recognition","canonicalPath":"/knowledge/synthetic-biology/mechanisms/guide-rna-and-pam-recognition","contentHash":"sha256:081073c605aee04950e56be34b76baf6419a1e11122e938f925900eb66c8042e","generatedAt":"2026-08-30T16:02:38.372Z","publicationDecision":{"recordId":"urn:maha:record:guide-rna-and-pam-recognition","publicEligible":true,"evaluatedAgainst":"maha-epistemic/1.0","reasons":[]},"claims":[{"id":"urn:maha:claim:guide-rna-and-pam-recognition","scope":"The constructs, biological systems, protocols, assays, datasets, and comparisons reported in A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.","boundary":"Sequence recognition rules do not by themselves predict chromatin access, cellular activity, or every off-target interaction.","claimKind":"empirical-claim","sourceIds":["source-jinek-cas9-2012"],"statement":"The cited experiments show that guide sequence and adjacent motif requirements condition Cas9 binding and cleavage in the reconstructed system.","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-jinek-cas9-2012","url":"https://www.science.org/doi/10.1126/science.1225829","title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","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":["Martin Jinek","Krzysztof Chylinski","Ines Fonfara","Michael Hauer","Jennifer A. Doudna","Emmanuelle Charpentier"],"boundary":"An in-vitro nuclease mechanism does not establish editing efficiency, specificity, delivery, safety, or phenotype in cells or organisms.","publisher":"Science","establishes":"The study reconstitutes RNA-programmed Cas9 cleavage in vitro and shows that a designed single-guide RNA can direct sequence-specific DNA cleavage adjacent to an appropriate motif.","identifiers":[{"value":"10.1126/science.1225829","scheme":"doi"}],"publishedAt":"2012-06-28","exactLocator":"Abstract; Figures 1–5; supplementary materials describing guide design and cleavage assays."}],"reviewEvents":[{"scope":"source-fidelity","verdict":"approve","reviewId":"epireview_a665cab511164fa1a068a031447e04b5","rationale":"Guide RNA and PAM recognition binds claim urn:maha:claim:guide-rna-and-pam-recognition only to A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity at PMC6286148 repository copy, Conclusions. The audit inspected repository-copy at bounded inspected artifact depth and recorded subject and claim support; the claim remains limited to “The constructs, biological systems, protocols, assays, datasets, and comparisons reported in A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.”. This decision applies only to record urn:maha:record:guide-rna-and-pam-recognition at sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:01:58.878Z","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":"sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"domain-fidelity","verdict":"approve","reviewId":"epireview_a67197134d9549a28c47610b1e63969b","rationale":"Guide RNA and PAM recognition remains within domain synthetic-biology. Its mechanism or method is the bounded proposition “The cited experiments show that guide sequence and adjacent motif requirements condition Cas9 binding and cleavage in the reconstructed system.”; the record does not transfer that proposition beyond Sequence recognition rules do not by themselves predict chromatin access, cellular activity, or every off-target interaction. This decision applies only to record urn:maha:record:guide-rna-and-pam-recognition at sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:01:58.972Z","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":"sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"boundary-adequacy","verdict":"approve","reviewId":"epireview_81036d624b9646ec8d5bda891cb2b71a","rationale":"Guide RNA and PAM recognition 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:guide-rna-and-pam-recognition at sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:01:59.061Z","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":"sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"rights-and-locator","verdict":"approve","reviewId":"epireview_d59718f57b7b46fc8fc787220fe3dc45","rationale":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity is identified by doi:10.1126/science.1225829, inspected at Abstract; Figures 1–5; supplementary materials describing guide design and cleavage assays., and retained under citation-with-paraphrase. This approval binds only exact revision sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7. This decision applies only to record urn:maha:record:guide-rna-and-pam-recognition at sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:01:59.144Z","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":"sha256:216a778cf1966d4c7e16153caa81e8432090e462c455f54e33fa72c0acc97fb7","supersedesReviewId":null,"reviewerProfileVersion":1}]}