ABSTRACT
I. INTRODUCTION A major goal of gene therapy is the stable delivery of therapeutic genes to human stem cells. The ability of a stem cell to both self-renew and repopulate a cell compartment makes it an obvious and attractive target for this type of therapy. Hematopoietic stem cells (HSCs) are the target of many gene therapy protocols largely because they are one of the most well-characterized human stem cells, are relatively accessible, and there are multiple diseases of the hematopoietic system which are good candidates for gene therapy approaches. To date, retroviral vectors have been the gene-delivery vehicle of choice for HSCs; in part because stable, long-term expression of therapeutic genes in human blood cells in vivo has already been demonstrated (1-3). This chapter will focus on the attempts which have been made to increase the ex vivo transduction efficiency of human HSCs with retroviral vectors, and it will review the progress on the development of the next generation of targetable retroviral vectors for in vivo gene transfer.
