Gene therapy: prospects for treatment of liver disease.

Gene therapy in the liver for treatment of metabolic diseases is a great challenge. The development of vectors for gene transfer to hepatocytes in vitro and to the liver in vivo has advanced very rapidly within the last few years. However, none of the existing vectors would allow for expression of therapeutic levels of a gene product for a longer period of time. Our laboratory is developing alternative strategies for gene transfer to the liver in vivo which are based on composite vectors consisting of envelopes and promoters derived from hepatitis B virus, an EBV-derived replicon, and the chromosomal protein HMG1. Hepatocyte specificity of both, binding of the particles and expression of foreign genes, was demonstrated.