Beyond Trikafta: new models to assess tissue dependent rescue of N1303K-CFTR.

ABSTRACT:

Rationale

Respiratory status of people with Cystic Fibrosis (pwCF) carrying N1303K is improved by Elexacaftor/Tezacaftor/Ivacaftor (ETI) but, contrary to other mutations, the impact on sweat test results is limited.

Methods

To explore this discrepancy, we implemented new sweat gland and respiratory cell lines stably expressing Wild type (WT)-, F508del- and N1303K-CFTR. CFTR dependent chloride (Cl^-) and bicarbonate (HCO₃-) transport was measured by short circuit current in these new models and in primary Human Nasal Epithelial Cells (HNECs). CFTR expression was evaluated by Western blot.

Results

In the airway and the sweat gland cells expressing F508del-CFTR, ETI induced maturation of CFTR and increased Cl^- transport. In the respiratory

SUBMITTER: Pranke I 

PROVIDER: S-EPMC12605165 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature