{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T20:25:03Z","timestamp":1792959903006,"version":"4.5.0"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK054759,HL152960,HL165404,75N92019C00010"],"award-info":[{"award-number":["DK054759,HL152960,HL165404,75N92019C00010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["ENGELH20XX2,ENGELH21XX0"],"award-info":[{"award-number":["ENGELH20XX2,ENGELH21XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,22]]},"abstract":"<jats:p>\n                    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (\n                    <jats:italic>CFTR<\/jats:italic>\n                    ) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor\/lumacaftor (VX-770\/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF. Using primary intestinal organoids and air-liquid interface cultures of airway epithelia, we demonstrate that the F508del mutation in ferret CFTR results in a severe folding and trafficking defect, which can be partially restored by treatment with CFTR modulators. In utero treatment of pregnant jills with ivacaftor\/lumacaftor prevented meconium ileus at birth in F508del kits and sustained postnatal treatment of CF offspring improved survival and partially protected from pancreatic insufficiency. Withdrawal of ivacaftor\/lumacaftor treatment from juvenile CF ferrets reestablished pancreatic and lung diseases, with altered pulmonary mechanics. These findings suggest that in utero intervention with a combination of CFTR modulators may provide therapeutic benefits to individuals with F508del. This\n                    <jats:italic>CFTR<\/jats:italic>\n                    -F508del ferret model may be useful for testing therapies using clinically translatable endpoints.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.157229","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T10:22:17Z","timestamp":1713867737000},"source":"Crossref","is-referenced-by-count":23,"title":["In utero and postnatal ivacaftor\/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets"],"prefix":"10.1172","volume":"9","author":[{"given":"Idil Apak","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingshen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, 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