LIPOSOME-MEDIATED CFTR GENE-TRANSFER TO THE NASAL EPITHELIUM OF PATIENTS WITH CYSTIC-FIBROSIS

We report the results of a double-blind, placebo-controlled trial in n ine cystic fibrosis (CF) subjects receiving cationic liposome complexe d with a complementary DNA encoding the CF transmembrane conductance r egulator (CFTR), and six CF subjects receiving only liposome to the na sal epithelium. No adverse clinical effects were seen and nasal biopsi es showed no histological or immuno-histological changes. A partial re storation of the deficit between CF and non-CF subjects of 20% was see n for the response to low Cl- perfusion following CFTR cDNA administra tion. This was maximal around day three and had reverted to pretreatme nt values by day seven. In some cases the response to low Cl- was with in the range for non-CF subjects. Plasmid DNA and transgene-derived RN A were detected in the majority of treated subjects. Although these da ta are encouraging, it is likely that transfection efficiency and the duration of expression will need to be increased for therapeutic benef it.