{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:20:49Z","timestamp":1787505649338,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal State Funded Research Institution \u201cResearch Centre for Medical Genetics\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>p.Asn1303Lys (N1303K) is a common missense variant of the CFTR gene, causing cystic fibrosis (CF). In this study, we initially evaluated the influence of CFTR modulators on the restoration of N1303K-CFTR function using intestinal organoids derived from four CF patients expressing the N1303K variant. The forskolin-induced swelling assay in organoids offered valuable insights about the beneficial effects of VX-770 + VX-661 + VX-445 (Elexacaftor + Tezacaftor + Ivacaftor, ETI) on N1303K-CFTR function restoration and about discouraging the prescription of VX-770 + VX-809 (Ivacaftor + Lumacaftor) or VX-770 + VX-661 (Ivacaftor + Tezacaftor) therapy for N1303K\/class I patients. Then, a comprehensive assessment was conducted on an example of one patient with the N1303K\/class I genotype to examine the ETI effect on the restoration of N1303K-CFTR function using in vitro the patient\u2019s intestinal organoids, ex vivo the intestinal current measurements (ICM) method and assessment of the clinical status before and after targeted therapy. All obtained results are consistent with each other and have proven the effectiveness of ETI for the N1303K variant. ETI produced a significant positive effect on forskolin-induced swelling in N1303K\/class I organoids indicating functional improvement of the CFTR protein; ICM demonstrated that ETI therapy restored CFTR function in the intestinal epithelium after three months of treatment, and the patient improved his clinical status and lung function, increased his body mass index (BMI) and reduced the lung pathogenic flora diversity, surprisingly without improving the sweat test results.<\/jats:p>","DOI":"10.3390\/ijms25052770","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T03:37:57Z","timestamp":1709091477000},"page":"2770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comprehensive Assessment of CFTR Modulators\u2019 Therapeutic Efficiency for N1303K Variant"],"prefix":"10.3390","volume":"25","author":[{"given":"Anna","family":"Efremova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-6371","authenticated-orcid":false,"given":"Nataliya","family":"Kashirskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"},{"name":"Moscow Regional Research and Clinical Institute (\u201cMONIKI\u201d), Moscow 129110, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Krasovskiy","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"},{"name":"Pulmonology Scientific Research Institute under Federal Medical and Biological Agency of Russian Federation, Moscow 115682, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-5532","authenticated-orcid":false,"given":"Yuliya","family":"Melyanovskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Krasnova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Mokrousova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Bulatenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-0407","authenticated-orcid":false,"given":"Elena","family":"Kondratyeva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Makhnach","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-256X","authenticated-orcid":false,"given":"Tatiana","family":"Bukharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":false,"given":"Rena","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Goldshtein","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jcf.2018.02.006","article-title":"ECFS Best Practice Guidelines: The 2018 Revision","volume":"17","author":"Castellani","year":"2018","journal-title":"J. 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