Liver-directed gene therapy: prospects and problems

The development of strategies for gene therapy in the liver is a challenging task because this organ is particularly involved in the manifestation of numerous genetic diseases as well as in malignant and infectious diseases. Most of the available techniques for gene transfer were already applied to hepatocytes ex vivo. Attempts to retransplant retrovirally transduced hepatocytes back to patients have shown the limits of the ex vivo approach. The obvious alternative would be the development of suitable techniques for gene transfer in vivo. Both viral and non-viral delivery systems were tested in animal models with limited success. This article summarizes the state of the art of the available techniques and vectors and discusses the essential future developments