EVALUATION OF HBV PROMOTERS FOR USE IN HEPATIC GENE-THERAPY

Strategies for in vivo hepatic gene therapy will require regulatory el ements which allow for long-term expression of therapeutic genes and r estriction of expression to hepatocytes, This study investigates the s uitability of promoters derived from hepatitis B virus (HBV) for liver -specific gene expression in vectors for hepatic gene therapy. We prov ide three hepatocyte-specific promoters, the HBV core promoter, the HB V core promoter linked directly to the HBV enhancer I, and a hybrid pr omoter containing the HSV enhancer II and a basic CMV promoter, which are hepatocyte-specific and allow for increasing levels of reporter ge ne expression, Moreover, in long-term expression studies using our pro moter constructs in the context of an EBV based expression system we f ound that expression from these promoters remained nearly unchanged ov er a period of at least two months in hepatocyte-derived cell lines.