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. 2021 Nov 19;11:22616. doi: 10.1038/s41598-021-02044-1

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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F508del/F508del CFTR nasal epithelia demonstrate low levels of spontaneously active CFTR-mediated ion transport that are slightly increased following 24 h VX-809/VX-770 treatment. Epithelia were analyzed in an Ussing chamber using the same methods as for non-CF epithelia, with the addition of acute 1 µM VX-770 between forskolin/IBMX (F/I) and CFTR(inh)-172 treatments for Panels (a–c). (a) Representative tracings of epithelia analyzed after treatment with vehicle vs. VX-809/VX-770. (b) Baseline values of transepithelial potential difference/voltage (V_te) and short-circuit current (I_SC) were normalized to the vehicle values in donor-matched replicate epithelia. (c) Responses to F/I or CFTR(inh)-172 [in the presence (+ F/I) or absence (-F/I) of F/I] treatments were normalized to the change in values in vehicle-treated epithelia. (d) Epithelia from a single donor were analyzed without acute VX-770 treatment (n = 3 replicates per condition). For Panels (b, c), n = 3 donors with 3 replicates per donor/condition. For data shown in Panel c, VX-809/VX-770 treatment resulted in significant increases in F/I and CFTR(inh)-172 for all cases (p < 0.003) with the exception of spontaneous CFTR-mediated changes in I_sc.