MDR 1 Gene Transfer to Hematopoietic Cells

Gene therapy, which has the potential to cure hereditary or acquired diseases, is still hampered by low gene expression in target organs. This is particularly true for hematopoietic disorders because the efficiency of gene transfer is limited and stable expression of transgenes in bone marrow has been found difficult to accomplish (Miller, 1990). In preclinical primate studies as well as in clinical trials, the percentage of hematopoietic cells expressing transgenes long-term have been found to be disappointingly low (Bodine et al., 1993; Dunbar et al., 1994; Van Beusechem et al., 1995). One possible strategy for overcoming this problem employs the use of selectable drug resistance markers, that allow enrichment of transduced cells in vivo, if or when expression levels decrease. Selectable markers provide an advantage to transduced cells by conferring resistance to cytotoxic drugs and result in the selected elimination of non-transduced cells by drug treatment.