Research of gene therapy for viral hepatitis using anti-sense DNA

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Asialoglycoprotein receptor mediated gene delivery is the most useful method for selective gene delivery to the hepatocytes. In vitro transfection of DNA to HepG2 cells, the transfection efficacy was highest at the carrier-DNA ratio of 480 : 1. Whne a lysosomal enzyme inhibitor, chloroquine was used for transfection into HepG2 cells, a 22-fold increase of efficacy was observed with addition of 50 mmol/L.The expression of transfered DNA-encoded products was observed in approximately 3% of HepG2 cells. When the carrier-^<32>P-labeled DNA complex was injected into the tail vessel of the mouse, most ^<32>P-labeled DNA were taken up by the liver. Microautoradiography of the live specimens after transfection of ^<35>S-labeled DNA indicated that the delivered DNA was located in the liver parenchymal cells.When the efficacy of gene delivery was tested in vivo, chloroquine effectively increased the efficacy. Moreover, the combination of chloroquine and intraportal injection strongly enhanced the in vivo transfection with asialoglycoprotein receptor mediated gene delivery.Thus, asialoglycoprotein receptor mediated gene transfer of anti-sense DNA is the selective gene delivery to the hepatocytes and may be the useful method of gene therapy for viral hepatitis.