Expression of introduced genetic sequences in hematopoietic cells following retroviral-mediated gene transfer

The use of retroviral vectors allows efficient transfer of genes into a variety of mammalian cells. A focus of research over the past 6 years has been the use of retroviral vectors to effect gene transfer into hematopoietic cells. These transduced cells might then be used for gene therapy of severe genetic diseases affecting blood cells. In spite of early optimism concerning the transfer and expression of a variety of gene sequences in hematopoietic cells, progress in obtaining the goal of stable and long-term expression of introduced genes in progeny of hematopoietic stem cells has been slow, frustrating, and only partially successful. This slow progress has been due, in part, to lack of understanding of the control of gene regulation in primary cells but also to the complexity of hematopoietic stem cell biology in both murine and large animal species. This review attempts to summarize the progress that has been made in the expression of genes introduced into hematopoietic cells and the difficulties still remaining before meaningful application of gene transfer methods can be expected to cure human diseases of bone marrow-derived cells.