Biol. Pharm. Bull. 28(8) 1472—1475 (2005)

cause hepatocytes synthesize a wide variety of proteins, perform a variety of post-translational modifications, and are involved in numerous diseases. Therefore, hepatocyte-targeted gene transfer would represent an important strategy for expanding treatment options for liver diseases. The successful gene expression in mouse hepatocytes in living animals was recently achieved by a rapid injection of a large amount of naked pDNA into a mouse tail vein (the hydrodynamicsbased procedure). Despite the many desirable features of the procedure such as simplicity, convenience, and high efficiency, this procedure is not suitable for the treatment of liver disease because it seriously damage the hepatocytes. We recently reported that a cationic liposomal vector, TFL-3 composed of a cationic lipid, DC-6-14, with helper lipids dioleoylphosphatidylethanolamine and cholesterol (1 : 0.75 : 0.75 molar ratio), achieved sufficient gene expression in primary cultured rat hepatocytes. Hence, TFL-3 may be a suitable vector system for successful gene expression in hepatocytes and it may be an attractive candidate for use in in vivo or ex vivo gene therapy. Among the currently available therapeutic options, hepatocyte transplantation is a promising procedure that could replace liver transplantation because it would overcome the shortage of available donors as well as a variety of technical difficulties. Therefore, a combination of hepatocyte transplantation and in vitro hepatocyte-targeted gene transfer using TFL-3, leading to the efficient expression of functional proteins, such as enzymes or growth factors, represent an important strategy for expanding the treatment options for liver disease. However, a widely applied approach to support cross-species is needed before human applications: the utility of TFL-3 on gene expression in non-dividing mammalian cells should be tested with different species. Therefore, in this study, we further examined the utility of TFL-3 on transgene expression in another rodent hepatocyte, namely primary cultured mouse hepatocytes. MATERIALS AND METHODS