ABSTRACT
This chapter reviews progress in preclinical gene therapy models and clinical gene therapy trials, and considers some of the most important issues limiting the clinical introduction of stem cell gene therapy. It outlines some of the areas for further research that may ultimately make this a routine option of medical treatment. The demonstration of retroviral vector transduction of murine hematopoietic progenitors provided the starting point for numerous preclinical models of stem cell gene therapy. There is extensive evidence in murine models that retroviral vectors can introduce foreign genes at high efficiency into hematopoietic progenitors and reconstituting stem cells. Genes that have been transferred and expressed in human hematopoietic cells via retroviral vectors include neomycin phosphotransferase, dihydrofolate reductase (DHFR) conferring resistance to methotrexate, β-globin, Adenosine Deaminase ADA, glucocerebrosidase, CD18, and argininosuccinate synthetase. The gene marking and gene therapy trials have shown that the introduction of new genetic information to the human hematopoietic system by recombinant retroviral vectors is feasible.
