Retroviral vector-mediated gene transfer into hematopoietic cells: prospects and issues.

Gene therapy is a developing technology that may allow the treatment of a variety of congenital and acquired genetic disorders as well as infectious diseases through the introduction of exogenous genetic material into relevant cellular populations. Currently, the most effective method for gene transfer into cells of the hematopoietic system is with retroviral vectors. Appropriate cellular targets for gene transfer include totipotent hematopoietic stem cells as well as long-lived lineage committed cells such as T lymphocytes. Although retroviral vector-mediated gene transfer into totipotent stem cells and subsequent long-term expression of transduced genetic material in stem cell progeny has been observed in murine bone marrow transplantation experiments, similar observations have not been made in clinically relevant large-animal models. A number of recent advances in gene delivery systems, purification of stem cells, defining extramedullary sources of stem cells, characterizing the biologic processes that regulate the proliferation and developmental potential of stem cells, and construction of more effective models for assessing stem cells, may result in improvements in gene transfer into large animal and human totipotent stem cells.