EVALUATION IN-VITRO AND IN-VIVO OF CATIONIC LIPOSOME-EXPRESSION CONSTRUCT COMPLEXES FOR CYSTIC-FIBROSIS GENE-THERAPY

We have tested the cationic liposome xy)propyl)-N,N,N-trimethyl-ammoni ummethylsulphate, (DOTAP), for gene delivery in vitro and in vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent dif ferences in the pattern and longevity of expression. Repeated administ ration was well tolerated. The potential for the transfer of foreign g enes into reproductive tissue was investigated by intravenous injectio n of DNA-DOTAP into female mice. Foreign DNA was undetectable in the o varies by Southern blot analysis at 1 and 7 days after injection. Our results suggest that DOTAP merits testing in cystic fibrosis patients for delivery of the cystic fibrosis transmembrane conductance regulato r (CFTR) gene to the respiratory tract and that substitution of the cy tomegalovirus (CMV) promoter for the simian virus (SV) promoter may im prove on the transitory response reported previously.