LONG-TERM IN-VIVO EXPRESSION OF THE MFG-ADA RETROVIRAL VECTOR IN RHESUS-MONKEYS TRANSPLANTED WITH TRANSDUCED BONE-MARROW CELLS

We have tested the recombinant human adenosine deaminase (hADA) retrov iral vector MFG-ADA for its efficacy in transducing hemopoietic stem c ells of nonhuman primates and its expression level in the hematopoieti c system, The percentage of provirus-positive granulocytes 1 year afte r transplantation of bone marrow transduced with MFG-ADA was 0.1%, whi ch was equivalent to previously obtained results with the hADA virus-p roducing cell line POC-1, However, in MFG-ADA monkeys, significantly m ore peripheral blood mononuclear cells carried the hADA gene (1% versu s 0.1%). Human ADA expression levels in peripheral blood mononuclear c ells were not different between POC-1 and MFG-ADA monkeys using sample s with equal numbers of provirus copies per cell, In contrast, in tota l red blood cell lysates of MFG-ADA monkeys, the hADA expression was h igher (similar to 10-fold) and could be detected longer (20 weeks and up to more than 1 year after bone marrow transplantation in 2 monkeys) than in POC-1 monkeys that were only positive for up to 12 weeks at t he most, At 3 years after bone marrow transplantation, the MFG-ADA pro virus could still be detected in 0.1% of bone marrow cells and periphe ral blood cells and in 1% of cultured T cells, These results show that MFG-ADA virus can give rise to long-term in vivo expression of hADA i n the primate hematopoietic system, However, transduction efficiencies remain low.