Gene transfer and bone marrow transplantation with special reference to Gaucher's disease

Gene therapy following gene transfer into hematopoietic cells is now being investigated for several genetic disorders (1). The candidate diseases under consideration and active experimental investigation are disorders that can be fully or partially corrected by allogeneic bone marrow transplantation, where the gene defect is known and the normal gene has been cloned and characterized. Together with ADA deficiency Gaucher's disease is a leading candidate among these disorders. We have developed high titer retroviral vectors containing the glucocerebrosidase gene that can transduce murine bone marrow stem cells with high efficiency and will result in high levels of human glucocerebrosidase in macrophages of long-term reconstituted mice. "Gene therapy" for Gaucher's disease has therefore been accomplished in the mouse. We have also developed high titer amphotropic vectors containing the glucocerebrosidase gene that can transduce human CD34+ hematopoietic progenitors with a high degree of efficiency. Up to 70% of CFU-GM colonies from these infected CD34+ cells contained the transferred gene as determined by PCR. Our vectors can also correct the enzyme deficiency of hematopoietic cells from Gaucher patients following gene transfer.