{"doi":"10.1126/science.ade1105","title":"Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease","abstract":"CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIIδ, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIIδ gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIIδ editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIIδ gene editing may thus represent a permanent and advanced strategy for heart disease therapy.","journal":"Science","year":2023,"id":315991,"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":121,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":258195,"name":"Francesco Chemello","orcid":"0000-0002-3877-527X","position":1,"is_corresponding":false},{"id":898268,"name":"Xurde M. Caravia","orcid":"0000-0002-1173-7003","position":2,"is_corresponding":false},{"id":251126,"name":"Wei Tan","orcid":"0000-0001-6008-3854","position":3,"is_corresponding":false},{"id":251166,"name":"Hui Li","orcid":"0000-0002-4114-8349","position":4,"is_corresponding":false},{"id":251163,"name":"Kenian Chen","orcid":"0000-0002-4083-841X","position":5,"is_corresponding":false},{"id":251167,"name":"Lin Xu","orcid":"0000-0001-5815-4457","position":6,"is_corresponding":false},{"id":251127,"name":"Ning Liu","orcid":"0000-0003-0257-1889","position":7,"is_corresponding":false},{"id":251128,"name":"Rhonda Bassel‐Duby","orcid":"0000-0001-7568-410X","position":8,"is_corresponding":false},{"id":225271,"name":"Eric N. Olson","orcid":"0000-0003-1151-8262","position":9,"is_corresponding":false},{"id":1018570,"name":"Simon Lebek","orcid":"0000-0003-4525-797X","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:06:32.274501Z","pmid":"36634166","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":[]}