Receptor-mediated interleukin-2 gene transfer into human hepatoma cells

Receptor-mediated gene delivery is an attractive method for gene transfer i n vitro and shows promise for in vivo gene therapy applications. In the cur rent study, we have selected the cytokine interleukin-2 (IL-2) gene to expl ore the feasibility of receptor-mediated gene transfer into human hepatocel lular carcinoma HepG2 cells, using Epstein-Barr virus (EBV)-based vectors. We have developed a targeted DNA delivery system for the treatment of liver cancer by gene therapy. This system utilizes the hepatocyte-specific asial oglycoprotein receptor, which is uniquely expressed on liver cell membranes but not present on other cell types. Galactosylated histone, a ligand to t he asialoglycoprotein receptors, was synthesized, and a new EBV-based expre ssion vector bearing the human IL-2 cDNA was constructed and conjugated to the ligand through ionic interactions. The ligand/IL-2 DNA complex was able to bind specifically to cell-surface receptors on the target cell and, whe n incubated with HepG2 cells, resulted in elevated levels of IL-2 gene expr ession. These results indicate that therapeutic genes like IL-2 in ligand/D NA complex can be transferred into hepatoma cells via the hepatocyte recept or. This study constitutes an encouraging first step in the assessment of r eceptor-mediated gene transfer as a technique for gene therapy in liver can cer.