Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.

ABSTRACT: Cystic fibrosis (CF) is a life-shortening disease affecting >160,000 individuals worldwide predominantly with respiratory symptoms. About 80% of individuals with CF have the p.Phe508del variant that causes the CF transmembrane conductance regulator (CFTR) protein to misfold and be targeted for premature degradation by the endoplasmic reticulum (ER) quality control (ERQC), thus preventing its plasma membrane (PM) traffic. Despite the recent approval of a "highly effective" drug rescuing p.Phe508del-CFTR, maximal lung function improvement is ∼14%. To identify global modulators of p.Phe508del traffic, we performed a high-content small interfering RNA (siRNA) microscopy-based screen of >9,000 genes and monitored p.Phe508del-CFTR PM rescue in human airway cells. This primary screen identified 2

SUBMITTER: Botelho HM 

PROVIDER: S-EPMC11876911 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature