enzyme defect In the patient's T lymphocytes alone may be sufficient to result 
In full immunologic reconstitution. Although we hope to deliver the ADA gene 
to self-renewing pluripotent bone marrow stem cells, several ADA ( - ) SC ID 
patients who have fully reconstituted by means of matched bone marrow 
transplantation have T cells as the only donor type cell remaining beyond the 
Immediate post transplant period. Thus, insertion of the ADA gene into the 
patient's T cells is a major emphasis of our work. 
A very wide range of ADA levels has been observed in different 
Individuals who have normal immune function. Heterozygotes for ADA deficiency 
are immunol oglcally normal despite having only 50? of the usual ADA levels. 
Rare Individuals (e.g.. the African !Kung tribesmen and several children found 
by screening In New York State) have been studied and found to have only 5-10? 
of normal ADA and yet are also Immunol ogical ly normal. Thus, it may not be 
necessary to achieve completely normal ADA levels by gene therapy to have a 
beneficial outcome. Similarly, a few Individuals have been described with ADA 
levels 40-50 times higher than normal In their erythrocytes (although normal 
levels In other cells). These patients have a mild form of hemolytic anemia 
but are also Immunol ogical ly normal. Therefore, expression of the transferred 
ADA gene several fold above the normal level might also be acceptable 
clinically. This very broad range of ADA gene expression in healthy 
Individuals suggests that a functioning ADA gene inserted via 
retroviral -mediated gene transfer need not be closely regulated for the 
procedure to benefit the patient. 
The gene for ADA has been cloned and is available as a cDNA. An essential 
requisite for any approach toward gene therapy is the demonstration that the 
Isolated gene and the delivery system proposed will actually correct the 
biochemical defect when used to treat the primary cells which express the 
Recombinant DNA Research, Volume 12 
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