Base editing and nanoparticle transfection of airway cell types essential for treatment of cystic fibrosis

ABSTRACT: Cystic Fibrosis (CF) is a life-limiting genetic disorder caused by deleterious variants in the CFTR gene that results in altered mucous impairing the airway epithelia. Durable correction of these variants in airway cells remain a therapeutic challenge for ~10% of individuals unresponsive to CFTR modulators. A common disease-causing CFTR splice site variant 3120+1G>A was corrected in primary CF airway cells using base editor RNAs. Single-cell RNA sequencing revealed a remarkable increase in detectable CFTR transcript in most CF airway epithelial cell types resulting in notable enrichment of CFTR-expressing ionocytes and secretory goblet cells. Progenitor basal cell subtypes were edited but they decreased as a fraction of total cells and CFTR expressing cells compared to unedited cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324177 | GEO | 2026/03/11

REPOSITORIES: GEO