Efficient Base Editing in Cystic Fibrosis Airway Epithelial Cells

Explore advanced gene therapy approaches for cystic fibrosis through this 24-minute webinar presented by Dr. Ashley Cooney. Learn how adenine base editors (ABE) offer a safer alternative to CRISPR/Cas9 by generating single-strand breaks rather than double-strand breaks to correct pathogenic CFTR gene variants like R553X and W1282X that are unresponsive to modulator therapies. Discover the innovative use of a single AAV vector with enhanced tropism for airway epithelia, combined with hypertonic saline formulation that remarkably enhances gene transfer by increasing ionic strength and improving stem cell transduction. Examine proof-of-concept work using the G551D CF pig model that recapitulates CF lung disease, demonstrating how base editing can permanently correct CFTR mutations in airway epithelial cells. Understand the mechanism by which ABE converts adenine to guanine nucleotides present in nonsense and missense variants, and learn about the clinical potential of hypertonic saline formulation given its established safety track record. Gain insights into overcoming the fundamental challenge of achieving sufficient transduction of airway epithelial cells for therapeutic correction in cystic fibrosis gene therapy, with applications extending to other genetic lung diseases including ABCA3 deficiency and surfactant protein B deficiency.