Gene therapy: current status and future directions.

Abstract

Of the many techniques which have been used to introduce new genes into cells, four are of particular interest for gene therapy. Transfection has been most extensively studied and has been used to put new genes into mice and men. Homologous recombination offers the promise of curing certain mutations in situ, but is still largely unexplored. Injection of new genes into the nuclei of single cell embryos has had startling successes in animals, but there are many scientific and ethical issues to be resolved before such an approach can be considered for gene therapy. Retroviral vectors currently offer the most exciting prospect for introducing useful gene sequences into defective cells; however, safety issues and problems of low levels of gene expression are still to be resolved. It appears likely that the bone marrow will be the first target of gene therapy for genetic diseases. The marrow is accessible and contains proliferating stem cells which can transmit the new genes to progeny cells. The possibility of treating enzyme deficiency diseases and hemoglobinopathies by gene transfer is attractive. Experiments in two patients with thalassemia major indicate that it is feasible to introduce new genes into bone marrow cells of man and return the modified cells to hematopoietic sites.