Development of HVJ-Liposome Mediated Gene Therapy Using HSV-Thymidine Kinase Gene for Hepatocellular Carcinoma

The suicide gene therapy for hepatocellular carcinoma (HCC) has given some promise, but the toxicity of adenovirusmediated gene delivery using the cytomegalovirus promoter (CMV) region linked to herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV) therapy was reported. In this study, to improve the technical issue of conventional gene therapy, we examined the usefulness of hemagglutinating virus of Japan (HVJ)-anionic-liposomemediated CMV-TK/GCV as an introductory target gene and development the selective application of alpha-fetoprotein (AFP) enhancer/promoter or heat shock protein (HSP) promoter for gene therapy. By the luciferase reporter gene assay, both HVJ-liposome transfection and the transcriptional activation of AFP enhancer/promoter or that of the HSP promoter by heat treatment were found to be quite effective in vivo and in vivo/in vitro models respectively. The toxicity of HVJ-anionic liposome-mediated gene therapy was smaller than that of adenovirus-driven approach as judged by histopathological examination of experimental animals\u27 liver and GPT blood test. Thus, the HVJ-liposome-mediated AFP-TK/GCV or HSPTK/ GCV technique may be a potent and useful strategy of the gene therapy of HCC