{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:35:04Z","timestamp":1787502904239,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Cystic Fibrosis Foundation (NCFS)","award":["HIT CF 3.0"],"award-info":[{"award-number":["HIT CF 3.0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The combination of the CFTR modulators elexacaftor, tezacaftor, and ivacaftor (ETI) enables the effective rescue of CFTR function in people with the most prevalent F508del mutation. However, the functional restoration of rare CFTR variants remains unclear. Here, we use patient-derived intestinal organoids (PDIOs) to identify rare CFTR variants and potentially individuals with CF that might benefit from ETI. First, steady-state lumen area (SLA) measurements were taken to assess CFTR function and compare it to the level observed in healthy controls. Secondly, the forskolin-induced swelling (FIS) assay was performed to measure CFTR rescue within a lower function range, and to further compare it to ETI-mediated CFTR rescue in CFTR genotypes that have received market approval. ETI responses in 30 PDIOs harboring the F508del mutation served as reference for ETI responses of 22 PDIOs with genotypes that are not currently eligible for CFTR modulator treatment, following European Medicine Agency (EMA) and\/or U.S. Food and Drug Administration (FDA) regulations. Our data expand previous datasets showing a correlation between in vitro CFTR rescue in organoids and corresponding in vivo ppFEV1 improvement upon a CFTR modulator treatment in published clinical trials, and suggests that the majority of individuals with rare CFTR variants could benefit from ETI. CFTR restoration was further confirmed on protein levels using Western blot. Our data support that CFTR function measurements in PDIOs with rare CFTR genotypes can help to select potential responders to ETI, and suggest that regulatory authorities need to consider providing access to treatment based on the principle of equality for people with CF who do not have access to treatment.<\/jats:p>","DOI":"10.3390\/ijms241914539","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T03:53:00Z","timestamp":1695700380000},"page":"14539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["CFTR Function Restoration upon Elexacaftor\/Tezacaftor\/Ivacaftor Treatment in Patient-Derived Intestinal Organoids with Rare CFTR Genotypes"],"prefix":"10.3390","volume":"24","author":[{"given":"Juliet W.","family":"Lefferts","sequence":"first","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3723-4615","authenticated-orcid":false,"given":"Marlou C.","family":"Bierlaagh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Kroes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha D. A.","family":"Nieuwenhuijze","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Centre for Living Technologies, Alliance TU\/e, WUR, UU, UMC Utrecht, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen N.","family":"Sonneveld van Kooten","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Centre for Living Technologies, Alliance TU\/e, WUR, UU, UMC Utrecht, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Niem\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibo F.","family":"Verburg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hettie M.","family":"Janssens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus Medical Center-Sophia Children\u2019s Hospital, University Hospital Rotterdam, 3015 CN Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-2831","authenticated-orcid":false,"given":"Danya","family":"Muilwijk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-196X","authenticated-orcid":false,"given":"Sam F. B.","family":"van Beuningen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Centre for Living Technologies, Alliance TU\/e, WUR, UU, UMC Utrecht, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis K.","family":"van der Ent","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Beekman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Wilhelmina Children\u2019s Hospital, University Medical Center, Utrecht University, 3584 EA Utrecht, The Netherlands"},{"name":"Regenerative Medicine Utrecht, University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Centre for Living Technologies, Alliance TU\/e, WUR, UU, UMC Utrecht, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.2772657","article-title":"Identification of the Cystic Fibrosis Gene: Chromosome Walking and Jumping","volume":"245","author":"Rommens","year":"1989","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/ng.2745","article-title":"Defining the Disease Liability of Variants in the Cystic Fibrosis Transmembrane Conductance Regulator Gene","volume":"45","author":"Sosnay","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","article-title":"CFTR Modulator Theratyping: Current Status, Gaps and Future Directions","volume":"18","author":"Clancy","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/14728214.2017.1418324","article-title":"An Update on New and Emerging Therapies for Cystic Fibrosis","volume":"22","author":"Hudock","year":"2017","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"00464","DOI":"10.1183\/23120541.00464-2022","article-title":"Dual CFTR Modulator Therapy Efficacy in the Real World: Lessons for the Future","volume":"8","author":"Dittrich","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a009761","DOI":"10.1101\/cshperspect.a009761","article-title":"Cystic Fibrosis Transmembrane Regulator Correctors and Potentiators","volume":"3","author":"Rowe","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1126\/science.ade2216","article-title":"Molecular Structures Reveal Synergistic Rescue of D508 CFTR by Trikafta Modulators","volume":"378","author":"Fiedorczuk","year":"2022","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cell.2021.12.009","article-title":"Mechanism of CFTR Correction by Type I Folding Correctors","volume":"185","author":"Fiedorczuk","year":"2022","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1126\/science.aaw7611","article-title":"Structural Identification of a Hotspot on CFTR for Potentiation","volume":"364","author":"Liu","year":"2019","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jcf.2011.12.005","article-title":"Ivacaftor Potentiation of Multiple CFTR Channels with Gating Mutations","volume":"11","author":"Yu","year":"2012","journal-title":"J. Cyst. Fibros."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S2213-2600(15)00201-5","article-title":"Efficacy and Safety of Ivacaftor in Patients with Cystic Fibrosis Who Have an Arg117His-CFTR Mutation: A Double-Blind, Randomised Controlled Trial","volume":"3","author":"Moss","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1056\/NEJMoa1409547","article-title":"Lumacaftor\u2013Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR","volume":"373","author":"Wainwright","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","article-title":"Tezacaftor\u2013Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del","volume":"377","author":"Munck","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","unstructured":"(2023, May 11). Kaftrio|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/kaftrio."},{"key":"ref_16","unstructured":"(2023, May 11). Trikafta: FDA-Approved Drugs, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&varApplNo=212273."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1513\/AnnalsATS.201708-668PS","article-title":"The U.S. Food and Drug Administration\u2019s Experience with Ivacaftor in Cystic Fibrosis: Establishing Efficacy Using in Vitro Data in Lieu of a Clinical Trial","volume":"15","author":"Durmowicz","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_18","unstructured":"(2023, August 01). Vertex Announces FDA Approvals of TRIKAFTA\u00ae (Elexacaftor\/Tezacaftor\/Ivacaftor and Ivacaftor), SYMDEKO\u00ae (Tezacaftor\/Ivacaftor and Ivacaftor) and KALYDECO\u00ae (Ivacaftor) for Use in People with CF with Certain Rare Mutations|Vertex Pharmaceuticals. Available online: https:\/\/investors.vrtx.com\/news-releases\/news-release-details\/vertex-announces-fda-approvals-trikaftar."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrg3849","article-title":"Cystic Fibrosis Genetics: From Molecular Understanding to Clinical Application","volume":"16","author":"Cutting","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jcf.2019.06.010","article-title":"Theranostics by Testing CFTR Modulators in Patient-Derived Materials: The Current Status and a Proposal for Subjects with Rare CFTR Mutations","volume":"18","author":"Amaral","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41467-023-36244-2","article-title":"Future Therapies for Cystic Fibrosis","volume":"14","author":"Allen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1247125","DOI":"10.1126\/science.1247125","article-title":"Organogenesisin a Dish: Modeling Development and Disease Using Organoid Technologies","volume":"345","author":"Lancaster","year":"2014","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nm.3201","article-title":"A Functional CFTR Assay Using Primary Cystic Fibrosis Intestinal Organoids","volume":"19","author":"Dekkers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 Stem Cells Build Crypt-Villus Structures in Vitro without a Mesenchymal Niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"344ra84","DOI":"10.1126\/scitranslmed.aad8278","article-title":"Characterizing Responses to CFTR-Modulating Drugs Using Rectal Organoids Derived from Subjects with Cystic Fibrosis","volume":"8","author":"Dekkers","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/thoraxjnl-2020-216368","article-title":"Rectal Organoid Morphology Analysis (ROMA) as a Promising Diagnostic Tool in Cystic Fibrosis","volume":"76","author":"Cuyx","year":"2021","journal-title":"Thorax"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2100508","DOI":"10.1183\/13993003.00508-2021","article-title":"Forskolin-Induced Organoid Swelling Is Associated with Long-Term Cystic Fibrosis Disease Progression","volume":"60","author":"Muilwijk","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/j.celrep.2019.01.068","article-title":"Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis","volume":"26","author":"Berkers","year":"2019","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1902426","DOI":"10.1183\/13993003.02426-2019","article-title":"Correction of CFTR Function in Intestinal Organoids to Guide Treatment of Cystic Fibrosis","volume":"57","author":"Ramalho","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1164\/rccm.202004-1200LE","article-title":"Comparison of Organoid Swelling and in Vivo Biomarkers of Cftr Function to Determine Effects of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation","volume":"202","author":"Graeber","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"246ra96","DOI":"10.1126\/scitranslmed.3008680","article-title":"Potentiator Ivacaftor Abrogates Pharmacological Correction of DF508 CFTR in Cystic Fibrosis","volume":"6","author":"Cholon","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jcf.2014.09.005","article-title":"Efficacy and Safety of Ivacaftor in Patients with Cystic Fibrosis and a Non-G551D Gating Mutation","volume":"13","author":"Munck","year":"2014","journal-title":"J. Cyst. Fibros."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1378\/chest.11-2672","article-title":"Ivacaftor in Subjects with Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation","volume":"142","author":"Flume","year":"2012","journal-title":"Chest"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"Efficacy and Safety of the Elexacaftor plus Tezacaftor plus Ivacaftor Combination Regimen in People with Cystic Fibrosis Homozygous for the F508del Mutation: A Double-Blind, Randomised, Phase 3 Trial","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1513\/AnnalsATS.201609-689OC","article-title":"Lumacaftor\/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR","volume":"14","author":"Rowe","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1056\/NEJMoa1709847","article-title":"Tezacaftor\u2013Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis","volume":"377","author":"Rowe","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bihler, H., Sivachenko, A., Millen, L., Bhatt, P., Patel, A.T., Chin, J., Bailey, V., Musisi, I., LaPan, A., and Allaire, N.E. (2023). In Vitro Modulator Responsiveness of 655 CFTR Variants Found in People With CF. bioRxiv.","DOI":"10.1101\/2023.07.07.548159"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1093\/hmg\/ddx367","article-title":"Mutation-Specific Downregulation of CFTR2 Variants by Gating Potentiators","volume":"26","author":"Avramescu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jcf.2018.02.007","article-title":"Comparison of ex vivo and in vitro intestinal cystic fibrosis models to measure CFTR-dependent ion channel activity","volume":"17","author":"Kruisselbrink","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Birimberg-Schwartz, L., Ip, W., Bartlett, C., Avolio, J., Vonk, A.M., Gunawardena, T., Du, K., Esmaeili, M., Beekman, J.M., and Rommens, J. (2023). Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis. Life Sci. Alliance, 6.","DOI":"10.26508\/lsa.202201857"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Railean, V., Rodrigues, C.S., Ramalho, S.S., Silva, I.A.L., Bartosch, J., Farinha, C.M., Pankonien, I., and Amaral, M.D. (2023). Personalized Medicine: Function of CFTR Variant p.Arg334Trp Is Rescued by Currently Available CFTR Modulators. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1155705"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"(2022). Rectal Organoid-Guided CFTR Modulator Therapy Restores Lung Function in a Cystic Fibrosis Patient with the Rare 1677delTA\/R334W Genotype. Eur. Respir. J., 60, 2201341.","DOI":"10.1183\/13993003.01341-2022"},{"key":"ref_44","unstructured":"Ramalho, A., Cuyx, S., Boon, M., Proesmans, M., Dupont, L., De Boeck, K., Verhulst, S., De Wachter, E., Van Biervliet, S., and Vermeulen, F. (2022, January 3\u20135). The Importance of CFTR MRNA Testing to Uncover Other Variants in CF Genotype That Affect CFTR Expression. Proceedings of the NACFC Philadelphia 2022, Philadelphia, PA, USA."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sadras, I., Kerem, E., Livnat, G., Sarouk, I., Breuer, O., Reiter, J., Gileles-Hillel, A., Inbar, O., Cohen, M., and Gamliel, A. (2023). Clinical and Functional Efficacy of Elexacaftor\/Tezacaftor\/Ivacaftor in People with Cystic Fibrosis Carrying the N1303K Mutation. J. Cyst. Fibros., online ahead of print.","DOI":"10.1016\/j.jcf.2023.06.001"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2202437","DOI":"10.1183\/13993003.02437-2022","article-title":"The French Compassionate Programme of Elexacaftor\/Tezacaftor\/Ivacaftor in People with Cystic Fibrosis with Advanced Lung Disease and No F508del CFTR Variant","volume":"61","author":"Burgel","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.xpro.2020.100019","article-title":"Protocol for Application, Standardization and Validation of the Forskolin-Induced Swelling Assay in Cystic Fibrosis Human Colon Organoids","volume":"1","author":"Vonk","year":"2020","journal-title":"STAR Protoc."},{"key":"ref_48","unstructured":"Labelbox Inc. (2023, September 13). Labelbox: The Leading Training Data Platform for Data Labeling. Available online: https:\/\/labelbox.com\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:58:13Z","timestamp":1760129893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":48,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914539"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914539","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}