biostudies-literatureBerical ANIDDK NIH HHSCystic Fibrosis FoundationNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | Center for Information TechnologyNIGMS NIH HHS4270https://www.ebi.ac.uk/biostudies/studies/S-EPMC9338271biostudies-literatureUnknown13(1)Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in inNature communicationsA multimodal iPSC platform for cystic fibrosis drug testing.PMC9338271P30 DK065988CFF HAWKIN20XX2CFF BERICA2010T32 GM133364R01 HL139799-04T32 HL007035R01 HL139799F31 HL158197Coote KLe Suer JAMahoney JLee REValley HMostoslavsky GThomas DRanallo NStuffer AHawkins FJHurley KPeasley MSeymour RRandell SHLu JBeermann MLBerical ABukis KHarrington JMcNally PMithal AfalseA multimodal iPSC platform for cystic fibrosis drug testing.Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in in2022-01-01T00:00:00Z2022 Jul2026-06-18T07:03:28.535Z2025-04-19T11:17:34.764ZS-EPMC93382713590621510.1038/s41467-022-31854-8