The development of retroviral vectors capable of efficient insertion of 
genes into manmalian hematopoietic cells (1-7) has generated interest in gene 
therapy as a potential approach for the treatment of lethal genetic disease 
(8,9). The cloning of a cDNA for the human adenosine deaminase enzyme (h-ADA) 
(10-12) has made the ADA deficient form of severe combined imnunodef iciency 
(SC ID) a potential candidate for such therapy. We recently described (13) a 
retroviral vector called SAX that contains the h-ADA cDNA (Figure 1). Using 
this vector, the h-ADA gene was transferred into ADA deficient human T cells 
that had been previously immortalized with human T cell leukemia virus 
(HTLV-1) . After gene transfer, the T cells produced the ADA enzyme from the 
new gene at levels similar to those seen in normal cells. This level of 
expression was sufficient to make the treated cells resistant to levels of 
deoxyadenosine that are toxic to untreated ADA deficient T cells in vitro (13). 
Therefore, the SAX retroviral vector appears to function efficiently in T cells 
cultured in vitro from ADA deficient patients. 
Severed, groups have attempted to establish in vivo models of h-ADA gene 
transfer in the mouse. Considerable success has been achieved in transferring 
the h-ADA gene into murine hematopoietic cells (14), and recently expression of 
this gene has been observed in CFU-S (15), but not yet in the fully 
reconstituted animal. To test the feasibility of a bone marrow transplant/ gene 
transfer approach in a large animal model more analogous to roan, we have 
developed a primate autologous transplantation model for the study of 
retroviral mediated ADA gene transfer into bone marrow cells. This report 
provides evidence for a low level of transfer and expression of the h-ADA gene 
in circulating hematopoietic cells in cyncmolgus monkeys for short periods of 
time. 
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Recombinant DNA Research, Volume 12 
