The results presented here indicate that viral-mediated gene therapy in treatment of chronic hepatitis B and HCC needs further optimization. However, treatment of the woodchucks with viral vectors allowed to achieve a long-lasting expression of the cytokines and their higher concentration preferably in the liver. Therefore, this strategy is proven to be more effective than an approach based on using of the soluble cytokines. In addition, adenovirusmediated gene transfer is proven to be a safe and a welltolerated strategy in the woodchucks.