{"doi":"10.1172/jci158287","title":"CRISPR/Cas therapeutic strategies for autosomal dominant disorders","abstract":"Autosomal dominant disorders present unique challenges, as therapeutics must often distinguish between healthy and diseased alleles while maintaining high efficiency, specificity, and safety. For this task, CRISPR/Cas remains particularly promising. Various CRISPR/Cas systems, like homology-directed repair, base editors, and prime editors, have been demonstrated to selectively edit mutant alleles either by incorporating these mutations into sgRNA sequences (near the protospacer-adjacent motif [\"near the PAM\"]) or by targeting a novel PAM generated by the mutation (\"in the PAM\"). However, these probability-based designs are not always assured, necessitating generalized, mutation-agnostic strategies like ablate-and-replace and single-nucleotide polymorphism editing. Here, we detail recent advancements in CRISPR therapeutics to treat a wide range of autosomal dominant disorders and discuss how they are altering the landscape for future therapies.","journal":"Journal of Clinical Investigation","year":2022,"id":253370,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":366691,"name":"Peter M. J. Quinn","orcid":"0000-0001-9940-4264","position":1,"is_corresponding":false},{"id":693621,"name":"Bruna Lopes da Costa","orcid":"0000-0002-6513-0717","position":2,"is_corresponding":false},{"id":299097,"name":"Stephen H. Tsang","orcid":"0000-0001-9082-2427","position":3,"is_corresponding":false},{"id":366689,"name":"Salvatore Marco Caruso","orcid":"0000-0003-1368-1178","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-19T00:24:55.325369Z","pmid":"35499084","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}