Retroviral Delivery of DNA into the Livers of Transgenic Mice Bearing Premalignant and Malignant Hepatocellular Carcinomas

ABSTRACT To develop gene therapy for hepatocellular carcinoma (HCC), we infused mice through the portal vein with retrovirus carrying the Escherichia coli β-galactosidase reporter gene under the transcriptional control of the viral long terminal repeat (LTR) and the promoter from the mouse multidrug resistance gene mdrlb. Two transgenic mouse HCC models were used, one bearing the human hepatitis B viral envelope protein and the other SV40 T antigen. These animals develop HCC with predictable pathological manifestations. The viral transduction efficiency appeared to depend upon the stage of the disease in the animals. The most efficient transduction occurred when the livers had developed microscopic nodular hyperplasia; in some cases as many as 0.01–0.1 copies/cell were transduced. The transduction efficiency was lower in the late stage of the disease when livers had a heavy tumor burden and in the early stage when no lesion was evident. Low viral transduction efficacy was also seen in nontransgenic animal...