Aerosol gene delivery in vivo.

The ability to express transgenes selectively within the lung will greatly facilitate the development of gene therapy for a variety of human diseases. We have demonstrated that aerosol administration of a chloramphenicol acetyltransferase (CAT) expression plasmid complexed to cationic liposomes produces high-level, lung-specific CAT gene expression in mice in vivo. Significant levels of CAT activity are seen in the lungs for at least 21 days following aerosolization. In situ immunostaining for intracellular CAT protein reveals that the majority of airway epithelial and alveolar lining cells are transfected in vivo. Histological analyses show no apparent treatment-related damage. These results have important implications for the development of human gene therapy.