We designed a novel technique for targeted gene transfer into the airway epithelium. This was constructed using multilamellar cationic liposomes, containing N-(α-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, phosphatidylcholine and cholesterol and fused with haemagglutinating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel vector to the airway of rats led to a highly efficient and widespread transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene into the bronchial epithelium and X alveolar macrophages, but not into the alveolar epithelium. The efficiency of gene transfer to the airway epithelium with a single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli, respectively (mean value, n = 6). Expression level of the luciferase gene delivered with this novel system was much higher than that without HVJ, in both the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles every other week resulted in minimal inflammatory infiltration in the subepithelial layer with no significant reduction in efficiency of the following gene transfer. We propose that this novel HVJ cationic liposome-mediated gene transfer system may be suitable for clinical gene therapy to treat subjects with lethal lung diseases such as cystic fibrosis.
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