NONINVASIVE LIPOSOME-MEDIATED GENE DELIVERY CAN CORRECT THE ION-TRANSPORT DEFECT IN CYSTIC-FIBROSIS MUTANT MICE

We report gene transfer to the Edinburgh insertional mutant mouse (cf/ cf), delivering CFTR cDNA-liposome complexes into the airways by nebul ization. We show full restoration of cAMP related chloride responses i n some animals and demonstrate, in the same tissues, human CFTR cDNA e xpression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf c ontrols. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for b oth the respiratory and intestinal tract following the liposome mediat ed gene delivery. The non-viral nature and potentially lower immunogen icity of DNA-liposomes suggest that this may offer a therapeutic alter native to adenoviral therapies.