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 intravenous or an airway route of administration. A plasmid containing the recombinant human alpha1-antitrypsin (halpha1AT) gene and a cytomegalovirus promoter complexed to cationic liposomes was given either intravenously or by aerosol to New Zealand White rabbits. Both routes of administration resulted in successful transfection and expression of the halpha1AT gene. halpha1AT mRNA and protein were detected for at least 7 days. Immunohistochemical staining showed halpha1AT protein in the pulmonary endothelium following intravenous administration, in alveolar epithelial cells following aerosol administration, and in the airway epithelium by either route. After intravenous injection of radiolabeled plasmids, autoradiographs showed localization of plasmid in endothelial cells, especially at arterial bifurcations, and at die alveolar level. A plasmid-liposome delivery system for gene therapy to the lungs may permit targeting of the DNA to subsets of lung cells by selection of the route of delivery and may permit a broad application of gene therapy to acute as well as chronic diseases.