Liposomes and viruses for gene therapy of cystic fibrosis.

Cystic fibrosis (CF) is a common, life-threatening autosomal recessive disease caused by mutations in the CFTR gene. It affects the function of the lung, gut, and liver. Present strategies for CF aim to correct the defect by introducing a normal copy of the CFTR gene into affected epithelial cells. Two vector systems have been proposed for gene therapy trials, replication defective adenovirus and cationic liposome/DNA complexes. Adenoviral vectors have been used in Phase I trials and in most cases give transient molecular and/or electrophysiological restitution of the ion transport cellular defects of CF. However, a dose of 10(9) pfu/ml applied to the lung led, in one patient, to a transient inflammatory reaction. New adenoviral vectors are presently being developed to solve this problem. Our studies using liposome/DNA complexes to deliver CFTR cDNA to the nasal epithelium were carried out in a double blind trial and showed no treatment-related local or general adverse reactions and significant small but transient correction of the ion transport defect. The results for both current approaches demonstrate the need for substantial improvement of the efficiency and duration of transgene expression to reach therapeutically relevant levels.