{"doi":"10.1073/pnas.2114858118","title":"Exon-skipping antisense oligonucleotides for cystic fibrosis therapy","abstract":"Significance Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, which can lead to respiratory failure. To date, there is no treatment for CF caused by the CFTR- W1282X mutation located on CFTR exon 23. Nonsense-mediated messenger RNA (mRNA) decay (NMD) degrades the CFTR- W1282X mRNA, leading to low levels of functional CFTR protein. We developed a cocktail of two antisense oligonucleotides (ASOs) that promotes the skipping of exon 23 of the CFTR- W1282X mRNA. The resulting mRNA is NMD resistant and preserves the reading frame. Its translation produces CFTR-Δex23 protein that improves CFTR activity in human bronchial epithelial cells. Our results set the stage for developing an ASO therapy for CF caused by the W1282X mutation.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":246404,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"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":806953,"name":"Nicole Sivetz","orcid":"0000-0002-0825-3622","position":1,"is_corresponding":false},{"id":806954,"name":"Jessica Layne","orcid":"0000-0003-3371-6796","position":2,"is_corresponding":false},{"id":479053,"name":"Dillon M. Voss","orcid":"0000-0001-7481-9455","position":3,"is_corresponding":false},{"id":806955,"name":"Lucia Yang","orcid":"0000-0002-7881-9724","position":4,"is_corresponding":false},{"id":806956,"name":"Qian Zhang","orcid":"0000-0001-6721-3594","position":5,"is_corresponding":false},{"id":576318,"name":"Adrian R. Krainer","orcid":"0000-0001-9024-9501","position":6,"is_corresponding":false},{"id":682467,"name":"Young Jin Kim","orcid":"0000-0003-1876-3359","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35017301","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":[]}