Single-dose lentiviral gene transfer for lifetime airway gene expression

Abstract

Background: Cystic fibrosis (CF) is caused by a defect in cystic fibrosis transmembrane conductance regulator (CFTR) activity, often resulting in an incurable airway disease. Gene therapy into the conducting airway epithelium is a potential cure for CF; however, most gene vectors do not result in longlived expression, and require re-dosing. Perversely, intrinsic host immune responses can then block renewed gene transfer. Methods: To investigate whether persistent gene expression could be achieved after a single dosing event, thus avoiding the issue of blocking host responses, we used a gene transfer protocol that combined an airway pretreatment using lysophosphatidylcholine with a human immu..