Gene therapy for human liver disease

Investigators working in the area of gene therapy believe the potential for advances in all medical disciplines is enormous. It is humbling, however to appreciate how far we need to go, as the field is truly in its infancy. Gene transfer technologies currently under evaluation in clinical trials have major limitations. Vector systems used in the clinics by the year 2000 probably have yet to be discovered. An additional lesson learned is that efforts at gene therapy are hampered by a lack of knowledge of the basic biology of the target organ and pathogenesis of the underlying disease. Successful gene therapy programs will critically evaluate the field and through fundamental research move steadily forward toward the long-term goal of truly effective therapy for a wide spectrum of disease. In the near future, two liver diseases are the most likely to be treated with gene therapy. The evaluation of patients with familial hypercholesterolemia is ongoing, and once approved, more candidates will be enrolled for therapy. Progress also has been made in creating vectors for the treatment of ornithine transcarbamylase deficiency. It remains to be seen whether adenoviruses or retroviruses will be used first in attempts to control this disease. Although the inflammatory response noted with current recombinant viruses is a formidable problem, the efficiency of gene transfer into the liver with these vectors makes continued study worthwhile.