Unraveling the Pharmacology of Disease-Causing CFTR Variants Using Automated Patch Clamp method for Theratyping.

Speaker: Frédéric Becq, University of Poitiers

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel encoded by the CFTR gene. Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by pathogenic CFTR variants that can disrupt multiple stages of CFTR biogenesis and function, including mRNA stability, protein folding, trafficking, and channel activity. More than 2,100 CFTR variants have been identified to date, although only a subset have been definitively established as disease-causing.

Theratyping refers to the functional characterization of disease-associated variants to determine whether, and to what extent, they respond to targeted therapies. This approach is particularly relevant for rare CFTR variants for which clinical evidence is limited or unavailable. In the context of CF, theratyping can therefore represent a key experimental component of a theranostic approach (a broader precision-medicine strategy that integrates diagnostic information with therapeutic decision-making). By leveraging the molecular and functional characteristics of an individual's CFTR variant, theratyping may help guide the selection of appropriate therapies, particularly when clinical evidence is insufficient.

Here, we describe the use of automated patch clamp electrophysiology with the Nanion Patchliner system as a tool to investigate the functional defects associated with disease-causing CFTR variants and to assess their correction by CFTR modulators.

Making Sense of Nonsense: ACE-tRNAs as Platform Therapeutics for Nonsense Mutations

Speaker: Dr. John Lueck, University of Rochester Medical Center

Real-time monitoring of epithelial resistance provides insights into CFTR function and responses to pharmacological modulation. This talk explores the use of the AtlaZ platform for continuous, label-free measurements of epithelial barrier properties and CFTR-dependent changes in impedance.

Using epithelial cell models expressing wild-type or F508del-CFTR, we examine responses to CFTR activation, inhibition, and modulator treatment, alongside comparisons with Ussing chamber recordings. These examples illustrate how impedance-based assays can complement established electrophysiological methods and support higher-throughput studies of CFTR variants and potential therapeutic compounds.