{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:26:31Z","timestamp":1790832391582,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["006048G223"],"award-info":[{"award-number":["006048G223"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["00022F220"],"award-info":[{"award-number":["00022F220"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["HASTING19GO"],"award-info":[{"award-number":["HASTING19GO"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD010662"],"award-info":[{"award-number":["OD010662"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>There is a major need for therapeutics that treat disease caused by premature termination codons (PTCs). Splice-switching antisense oligonucleotides (ASOs) can be directed to block splicing and cause exon skipping, a process that can be used to\u00a0effectively remove PTCs from an mRNA. This ASO-induced exon skipping can restore protein coding potential when the exons on either side of the skipped exon are in the same reading frame, or symmetrical. We demonstrate the potential of this\u00a0approach as a therapeutic\u00a0using the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, which has CF-associated, PTC-causing variants in all 27 of its exons. We functionally screened all CFTR isoforms that can be generated by\u00a0deletion of symmetrical exons and identify four that are functionally responsive to CFTR modulators. We identified ASOs that induce skipping of these exons and show that they recover CFTR function in airway cells derived from individuals with CFTR PTC variants. This study demonstrates that systematic functional analysis of in-frame exon-deleted protein isoforms can successfully identify targets for ASO-based splice-switching therapies, a therapeutic concept that can be broadly applied to any multi-exon protein-coding gene disrupted by PTCs.<\/jats:p>","DOI":"10.1093\/narmme\/ugae017","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T11:56:54Z","timestamp":1730980614000},"source":"Crossref","is-referenced-by-count":3,"title":["Systematic deletion of symmetrical <i>CFTR<\/i> exons reveals new therapeutic targets for exon skipping antisense oligonucleotides"],"prefix":"10.1093","volume":"1","author":[{"given":"Cecilia","family":"Pena-Rasgado","sequence":"first","affiliation":[{"name":"Center for Genetic Diseases, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]},{"name":"Compound Screening and Drug Discovery Core, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvia","family":"Rodriguez-Manriquez","sequence":"additional","affiliation":[{"name":"Center for Genetic Diseases, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]},{"name":"Compound Screening and Drug Discovery Core, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-9961","authenticated-orcid":false,"given":"Miroslav","family":"Dundr","sequence":"additional","affiliation":[{"name":"Center for Cancer Cell Biology, Immunology and Infection, Chicago Medical School, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago , IL 60064 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u00a0J","family":"Bridges","sequence":"additional","affiliation":[{"name":"Center for Genetic Diseases, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-9261","authenticated-orcid":false,"given":"Michelle\u00a0L","family":"Hastings","sequence":"additional","affiliation":[{"name":"Center for Genetic Diseases, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]},{"name":"Department of Pharmacology, University of Michigan Medical School , 1150 W Medical Center Dr,\u00a0Ann Arbor, MI 48109,","place":["USA"]},{"name":"Department of Medicinal Chemistry, University of Michigan College of Pharmacy , 1150 W Medical Center Dr,\u00a0 Ann Arbor , MI 48109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-7956","authenticated-orcid":false,"given":"Wren\u00a0E","family":"Michaels","sequence":"additional","affiliation":[{"name":"Center for Genetic Diseases, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]},{"name":"Compound Screening and Drug Discovery Core, Rosalind Franklin University of Medicine and Science , 3333 Green Bay Rd, North Chicago, IL 60064,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"2025010217125432900_B1","doi-asserted-by":"crossref","DOI":"10.1007\/s12033-024-01062-4","article-title":"Messenger RNA surveillance: current understanding, regulatory mechanisms, and future implications","author":"Das","year":"2024","journal-title":"Mol. 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