We plan to compare the lentiviral and foamy virus vector systems with respect to relative efficiency of gene transfer into primitive human hematopoietic cells. Various substances e.g., Fibroblast Growth Factor -1 and Wnt 3A, that have been reported to cause expansion of primitive murine hematopoietic cells will also be evaluated for their effects of primitive human hematopoietic cells in culture. Another focus is the comparison of various globin gene vectors with respect to the relative levels of globin gene expression in differentiating erythroid cells. Finally, the impact of cryopreservation on viability and engraftment potential of primitive hematopoietic cells will be assessed. This research proposal will provide preclinical data that will aid in the development of treatment strategies for genetic diseases, specifically hemoglobin disorders, based on gene transfer into repopulating stem cells.