Propellant-driven aerosols of DNA plasmids for gene expression in the respiratory tract

ABSTRACT Delivery of therapeutic DNA molecules to the respiratory tract is of great interest but has been limited to instillation or aerosolization of DNA-coated liposomes or virusvectored genes in aqueous solutions. We have developed propellant-driven aerosols to deliver metered doses of DNA to the respiratory tract. Plasmid DNA was combined with surfactants to suspend it in a propellant. When aerosolized, respirable-sized DNA particles were produced. Aerosols of a β-galactosidase–containing plasmid induced transfection and gene expression in the respiratory epithelial cells of aerosolexposed mice. Metered-dose, propellant-driven aerosols of DNA offer a new approach to delivering therapeutic genes or DNA-based vaccines to the respiratory tract.