{"doi":"10.1093/nar/gkab788","title":"Functional correction of<i>CFTR</i>mutations in human airway epithelial cells using adenine base editors","abstract":"Mutations in the CFTR gene that lead to premature stop codons or splicing defects cause cystic fibrosis (CF) and are not amenable to treatment by small-molecule modulators. Here, we investigate the use of adenine base editor (ABE) ribonucleoproteins (RNPs) that convert A•T to G•C base pairs as a therapeutic strategy for three CF-causing mutations. Using ABE RNPs, we corrected in human airway epithelial cells premature stop codon mutations (R553X and W1282X) and a splice-site mutation (3849 + 10 kb C > T). Following ABE delivery, DNA sequencing revealed correction of these pathogenic mutations at efficiencies that reached 38-82% with minimal bystander edits or indels. This range of editing was sufficient to attain functional correction of CFTR-dependent anion channel activity in primary epithelial cells from CF patients and in a CF patient-derived cell line. These results demonstrate the utility of base editor RNPs to repair CFTR mutations that are not currently treatable with approved therapeutics.","journal":"Nucleic Acids Research","year":2021,"id":155371,"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":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":657968,"name":"Soumba Traore","orcid":null,"position":1,"is_corresponding":false},{"id":378027,"name":"Ashley L. Cooney","orcid":"0000-0003-2717-9138","position":2,"is_corresponding":false},{"id":657969,"name":"Christian M. Brommel","orcid":null,"position":3,"is_corresponding":false},{"id":294324,"name":"Katarina Kulhánková","orcid":"0000-0001-7189-2323","position":4,"is_corresponding":false},{"id":259937,"name":"Patrick L. Sinn","orcid":"0000-0002-9746-966X","position":5,"is_corresponding":false},{"id":254240,"name":"Gregory A. Newby","orcid":"0000-0001-7869-2615","position":6,"is_corresponding":false},{"id":32147,"name":"David R. Liu","orcid":"0000-0002-9943-7557","position":7,"is_corresponding":false},{"id":225536,"name":"Paul B. McCray","orcid":"0000-0002-4067-577X","position":8,"is_corresponding":false},{"id":379563,"name":"Sateesh Krishnamurthy","orcid":null,"position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-18T23:43:59.154159Z","pmid":"34520545","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":[]}