In vivo gene transduction in hepatoma using monoclonal antibody or specific promotor.

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Most viral vectors are highly immunogenic and are of limited use for somatic gene therapy that requires repetitive administrations. We developed a highly efficient gene transduction procedure useful for repetitive transfection using HVJ-liposome. We revealed that LacZ gene was deliveredto and expressed with high effeciency to rat liver. Antibody response to HVJ-liposome or cytotoxic T lymphocyte were not elicited against autologous rat hepatocyte. Using genetrasduction method, we performed gene therapy for liver cirrhosis using hepatocyte growth factor (HGF) and for hepatocellular carcinoma (HCC) by HSV-TK gene. Established liver cirrhosis rat model which has been induced by dimethy lnitrosamine was treated with muscle directed HGF gene therapy. HGF protein was detected in the plasma of rats, and tyrosine phosphorylation of c-Met/HGF receptor was observed. Fibrous component in the cirrhotic liver disappeared and the mortality was completely abrogated in HGF gene transducted rats. Transgene of HSV-TK gene under the control of alpha-fetoprotein (AFP) promotor achieved tumor regression for AFP-producing human HCC tumor in athymic nude mice. The suicidal gene, HSV-TK,was specifically expressed in the AFP-producing cells but not in normal cells. These results indicated that these gene therapies can be novel molecular approaches for liver cirrhosis and for HCC.