NO LUNG TOXICITY AFTER REPEATED AEROSOL OR INTRAVENOUS DELIVERY OF PLASMID-CATIONIC LIPOSOME COMPLEXES

The safety aspects of human gene therapy are of paramount importance i n developing an ideal system for gene transfer. Lipofection using DNA in the form of a plasmid has been shown to successfully transfect the lungs when administered either intravenously or by aerosol. We have sh own that repeated intravenous or aerosol administration of a plasmid c ontaining the recombinant human alpha(1)-antitrypsin gene and a cytome galovirus promoter complexed to cationic liposomes results in no adver se effects on pulmonary histology, lung compliance, lung resistance, o r alveolar-arterial oxygen gradient. Immunohistochemistry and Western blot analysis confirm successful gene transfer using this delivery sys tem. We conclude that plasmids complexed to cationic liposomes may be a safe and efficacious delivery system for in vivo gene transfer to th e lungs. Using this delivery system, in vivo gene therapy to the lungs can be achieved by either intravenous or aerosol administration of th e transgene.