AAVB5-ABEpG551D

AAVB5-ABEpG551D is an experimental gene therapy candidate designed for the treatment of cystic fibrosis (CF) caused by the G551D mutation in the CFTR gene. The therapeutic utilizes a novel, airway-tropic adeno-associated virus (AAV) capsid, AAVB5, to deliver a single-vector cassette encoding an adenine base editor (ABE). This ABE employs a Staphylococcus aureus Cas9 (SaCas9) KKH variant to enable precise A-to-G conversion at the endogenous CFTR genomic locus, effectively correcting the mutant aspartic acid (D) back to the wild-type glycine (G). Developed through a collaboration involving the University of Iowa, the Children's Hospital of Philadelphia, and the Broad Institute, AAVB5-ABEpG551D is formulated in hypertonic saline to enhance delivery to airway epithelial cells, including basal cells, aiming to provide a durable and permanent correction of anion transport in patients who are ineligible for or intolerant of standard CFTR modulators.