PERSISTENT GENE-EXPRESSION IN RAT-LIVER IN-VIVO BY REPETITIVE TRANSFECTIONS USING HVJ-LIPOSOME

Most viral vectors are highly immunogenic and are of limited use for s omatic gene therapy that requires repetitive administrations. We have developed a highly efficient gene transduction procedure useful for re petitive transfections using liposome containing hemagglutinating viru s of Japan (HVJ-liposome). The Escherichia coli beta-galactosidase (be ta-gal) gene was embodied in HVJ-liposome, and introduced directly int o the caudal lobe of rat liver that was transiently isolated from a sy stemic circulation. A 116 kDa beta-gal protein was detected in transfe cted rat liver tissues by Western blot analysis and it was expressed i n more than two-thirds of the liver by histological staining. It was f ound that the transfection efficiency was not affected by repetitive t ransfections. In support of these findings, antibody response to HVJ-l iposome detected in the rat sera was weak and transient. Furthermore, cytotoxic T lymphocytes were not elicited against autologous rat hepat ocytes that were transfected in vivo using HVJ-liposome. Thus, our res ults demonstrate that the isolation of a target liver from systemic ci rculation and the direct administration of foreign genes using HVJ-lip osomes are useful for high gene transduction and persistent gene expre ssion in the liver.