{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:20:30Z","timestamp":1784290830311,"version":"3.55.0"},"reference-count":17,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government of Canada through Genome Canada and Ontario Genomics Institute","award":["OGI-148"],"award-info":[{"award-number":["OGI-148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>It has been suggested that in vitro studies of the rescue effect of CFTR modulator drugs in nasal epithelial cultures derived from people with cystic fibrosis have the potential to predict clinical responses to the same drugs. Hence, there is an interest in evaluating different methods for measuring in vitro modulator responses in patient-derived nasal cultures. Commonly, the functional response to CFTR modulator combinations in these cultures is assessed by bioelectric measurements, using the Ussing chamber. While this method is highly informative, it is time-consuming. A fluorescence-based, multi-transwell method for assaying regulated apical chloride conductance (Fl-ACC) promises to provide a complementary approach to theratyping in patient-derived nasal cultures. In the present work, we compared Ussing chamber measurements and fluorescence-based measurements of CFTR-mediated apical conductance in matching, fully differentiated nasal cultures derived from CF patients, homozygous for F508del (n = 31) or W1282X (n = 3), or heterozygous for Class III mutations G551D or G178R (n = 5). These cultures were obtained through a bioresource called the Cystic Fibrosis Canada-Sick Kids Program in Individual CF Therapy (CFIT). We found that the Fl-ACC method was effective in detecting positive responses to interventions for all genotypes. There was a correlation between patient-specific drug responses measured in cultures harbouring F508del, as measured using the Ussing chamber technique and the fluorescence-based assay (Fl-ACC). Finally, the fluorescence-based assay has the potential for greater sensitivity for detecting responses to pharmacological rescue strategies targeting W1282X.<\/jats:p>","DOI":"10.3390\/cells12081174","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T01:34:15Z","timestamp":1681695255000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Correlation of Electrophysiological and Fluorescence-Based Measurements of Modulator Efficacy in Nasal Epithelial Cultures Derived from People with Cystic Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7714-8095","authenticated-orcid":false,"given":"Tarini N. A.","family":"Gunawardena","sequence":"first","affiliation":[{"name":"Program of Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Boz\u00f3ky","sequence":"additional","affiliation":[{"name":"Providence Health Care, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3690-8956","authenticated-orcid":false,"given":"Hong","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D. W.","family":"Eckford","sequence":"additional","affiliation":[{"name":"Program of Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-6601","authenticated-orcid":false,"given":"Theo J.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Paediatrics, Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4057-6592","authenticated-orcid":false,"given":"Felix","family":"Ratjen","sequence":"additional","affiliation":[{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Paediatrics, Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Gonska","sequence":"additional","affiliation":[{"name":"Program of Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Bear","sequence":"additional","affiliation":[{"name":"Program of Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","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_2","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":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"e202000940","DOI":"10.26508\/lsa.202000940","article-title":"Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids","volume":"4","author":"Geurts","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1164\/rccm.201808-1436LE","article-title":"Might Brushed Nasal Cells Be a Surrogate for CFTR Modulator Clinical Response?","volume":"199","author":"Pranke","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sermet-Gaudelus, I., Nguyen-Khoa, T., Hatton, A., Hayes, K., and Pranke, I. (2021). Sweat Chloride Testing and Nasal Potential Difference (NPD) Are Primary Outcome Parameters in Treatment with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080729"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jcf.2018.03.013","article-title":"The CF Canada-Sick Kids Program in individual CF therapy: A resource for the advancement of personalized medicine in CF","volume":"18","author":"Eckford","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1165\/rcmb.2019-0384OC","article-title":"Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy","volume":"63","author":"Lee","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e202101320","DOI":"10.26508\/lsa.202101320","article-title":"Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia","volume":"5","author":"Amatngalim","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1177\/1087057113488420","article-title":"A rapid membrane potential assay to monitor CFTR function and inhibition","volume":"18","author":"Maitra","year":"2013","journal-title":"J. Biomol. 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Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1038\/s41598-017-07504-1","article-title":"Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators","volume":"7","author":"Pranke","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1073\/pnas.0135434100","article-title":"A macromolecular complex of beta 2 adrenergic receptor, CFTR, and ezrin\/radixin\/moesin-binding phosphoprotein 50 is regulated by PKA","volume":"100","author":"Naren","year":"2003","journal-title":"Proc. Natl. Acad. Sci. 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