Nontechnical Abstract 
ADA Deficiency is a fatal genetic disease that often 
results in death within the first years of life. The disease is 
characterized by a loss of immune cells (the lymphocytes) in the 
body and this results in a profound immunodeficiency, called 
Severe Combined Immunodeficiency (SCID) . The disease is caused 
by a defect in one of the genes that is required for the proper 
functioning of the T lymphocytes. The treatment of choice is a 
matched bone marrow transplantation. But for those patients who 
are not candidates for bone marrow transplantation, we propose to 
attempt to provide immune protection by using gene therapy. The 
procedure would be to remove T lymphocytes from patients who are 
on PEG-ADA, grow the T cells in tissue culture, insert a normal 
ADA gene into them using a process called retroviral-mediated 
gene transfer, and then return the gene-corrected cells to the 
patient. 
The protocol is designed to have two parts. In Part 1, 
low numbers of gene-corrected T lymphocytes would be given to the 
patient repeatedly in order to build up the immune system and 
also to obtain information as to how long gene-corrected T cells 
survive. In Part 2A, a selection procedure would be used to 
increase the number of gene-corrected T cells making substantial 
amounts of the ADA enzyme. These enriched cells would then be 
given to the patient monthly for approximately six months. In 
Part 2B, the number of gene-corrected T cells would be escalated 
to the predicted therapeutic level (probably around 1 billion 
gene-corrected T cells per kilogram body weight of the patient) . 
Then, 1 to 3 billion gene-corrected T cells per kg would be 
infused several times and the patient would be monitored in order 
to determine if significant clinical improvement has occurred. 
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Recombinant DNA Research, Volume 14 
