AEROSOL AND INTRAVENOUS TRANSFECTION OF HUMAN ALPHA-1-ANTITRYPSIN GENE TO LUNGS OF RABBITS

In vivo gene transfer to the lungs is possible either by an intravenou s or an airway route of administration. A plasmid containing the recom binant human alpha1-antitrypsin (halpha1AT) gene and a cytomegalovirus promoter complexed to cationic liposomes was given either intravenous ly or by aerosol to New Zealand White rabbits. Both routes of administ ration resulted in successful transfection and expression of the halph a1AT gene. halpha1AT mRNA and protein were detected for at least 7 day s. Immunohistochemical staining showed halpha1AT protein in the pulmon ary endothelium following intravenous administration, in alveolar epit helial cells following aerosol administration, and in the airway epith elium by either route. After intravenous injection of radiolabeled pla smids, autoradiographs showed localization of plasmid in endothelial c ells, especially at arterial bifurcations, and at die alveolar level. A plasmid-liposome delivery system for gene therapy to the lungs may p ermit targeting of the DNA to subsets of lung cells by selection of th e route of delivery and may permit a broad application of gene therapy to acute as well as chronic diseases.