Section Review: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: A perspective on gene therapy for cystic fibrosis

Abstract

Following the cloning of the cystic fibrosis gene, in vitro studies rapidly established the feasibility of gene therapy. Clinical gene transfer safety and efficacy trials have already been initiated in the US and UK. Whilst a variety of gene transfer vectors are potentially available for use in gene transfer trials, adenovirus vectors and cationic liposomes have shown the most promise thus far. Adenoviruses have been shown to be efficient in vitro and, in some species, in vivo. However, immunologic responses may severely limit the utility of adenovirus-mediated gene therapeutic approaches for cystic fibrosis. Cationic liposomes may have a better safety profile and appear to be as efficient as adenovirus vectors in initial reports from clinical trials. However, the lack of consistent and full functional correction of Cl− transport in published data from clinical trials suggests that the presently used adenovirus vectors and cationic liposomes may not be sufficiently efficient to offer a true clinical benefit at this time. Adeno-associated virus vectors may soon enter human clinical trials and retroviruses have recently begun to show promise for cystic fibrosis gene therapy. Hence, efforts should be pursued to improve these vectors further as well as to develop new, more efficient vectors with improved safety profiles.