HVJ (SENDAI VIRUS)-CATIONIC LIPOSOMES - A NOVEL AND POTENTIALLY EFFECTIVE LIPOSOME-MEDIATED TECHNIQUE FOR GENE-TRANSFER TO THE AIRWAY EPITHELIUM

We designed a novel technique for targeted gene transfer into the airw ay epithelium. This was constructed using multilamellar cationic lipos omes, containing lpha-trimethylammonioacetyl)-didodecyl-D-glutamate ch loride, phosphatidylcholine and cholesterol and fused with haemaggluti nating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aer osol delivery of this novel vector to the airway of rats led to a high ly efficient and widespread transduction of fluorescein isothiocyanate -labeled oligonucleotides or lacZ gene into the bronchial epithelium a nd alveolar macrophages, but not into the alveolar epithelium. The eff iciency of gene transfer to the airway epithelium with a single admini stration 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 withou t HVJ, in bath the trachea and lung tissue. Two pretreatment HVJ-catio nic liposome vehicles every other week resulted in minimal inflammator y infiltration in the subepithelial layer with no significant reductio n in efficiency of the following gene transfer. We propose that this n ovel HVJ cationic liposome-mediated gene transfer system may be suitab le for clinical gene therapy to treat subjects with lethal lung diseas es such as cystic fibrosis.