A novel liver-directed gene delivery system using an autonomously replicating vector specifically expressed in AFP positive hepatoma cells

A composite EBV-based expression vector, pEBAF, was constructed with the 5′-flanking sequence of human α-fetoprotein gene as a promoter. Complexed to galactosylated histone, this vector with a foreign DNA insertion could be transferred into hepatic ceils via the asialoglycoprotein receptor mediated endocytosis pathway. It was replicated as an episome, and its expression was restricted to the AFP positive hepatoma cells. This new gene delivery method has the following advantages: (i) absence of a potential toxicity is related to viral vectors; (ii) the targeting is specific to AFP positive hepatoma cells; (iii) the introduction of the EBV replicon into this system results in the highlevel expression and long-term maintenance of the transferred gene. This novel gene delivery system has potential applications in gene therapy for the treatment of hepatocellular carcinoma. Project supported by the National High Technology Development Program and partly by National Climbing Project.