Gene therapy progress and prospects: cystic fibrosis

Abstract

Since the cloning of the cystic fibrosis gene (CFTR) in 1989, 18 clinical trials have been carried out, including five in the 2 years reviewed here. Most trials demonstrated proof-of-principle for gene transfer to the airway. However, gene transfer efficiency with each of the three gene transfer agents (adenovirus (Ad), adeno-associated virus 2 (AAV2) and cationic liposomes) was low, and most likely insufficient to achieve clinical benefit. Here, we will review the clinical and pre-clinical progress for the last 2 years (2000-2001) and briefly speculate on future prospects for the next 2 in CF gene therapy.

Figure 1

Scanning electron micrograph of human airway epithelium showing fields of cilia covered at their tips by flakes of mucus. In hypersecretory disease the mucus usually forms a continuous sheet or ‘blanket’ overlying the cilia (supplied by courtesy of Professor Peter Jeffery, Imperial College, London, UK).

Figure 2

Viral gene transfer to the lung. (a) Recombinant Sendai virus (SeV) mediated β-galactosidase expression 48 h after gene transfer. (b) Filovirus pseudotyped lentivirus-mediated β-galactosidase expression 63 days after gene transfer (with permission from ^{Ref. 33})..