Hepatocyte transplantation and gene therapy.

Trials of liver-directed gene therapy are a clinical reality. Technology is rapidly developing for the isolation of large numbers of human hepatocytes. Recombinant DNA techniques are available to engineer recombinant retroviruses which express genes of clinical relevance. Familial hypercholesterolemia serves as the clinical paradigm for liver-directed gene therapy, and the clinical protocol is underway. Early results are promising. Techniques for hepatocyte delivery, optimization of gene transfer, and safety considerations are important considerations in designing a human trial. Other diseases which are likely to be among the first treated with this new approach are ornithine transcarbamylase deficiency, hemophilia B, and Crigler-Najjar syndrome.