genetic abnormality. As will be discussed in section I.B.2., we have developed 
a retroviral delivery system that efficiently transfers a functioning ADA gene 
to T cell lines derived from patients with ADA deficiency. Following gene 
transfer, these cells express normal levels of human ADA and the hypersensi- 
tivity of these T cells to toxicity by deoxyadenosine. a principal pathologic 
consequence of ADA deficiency, is corrected. Thus, corrected cells should have 
a selective growth advantage in the patient and. consequently, no cytoablation 
of the patient's own marrow would be necessary. For this selective advantage 
to be effective, however, the ADA gene would need to be expressed not only in 
the mature T cell, but also in the stem cell and throughout all stages of T 
cell differentiation. At present there are no experimental results that 
address whether or not gene expression will be maintained jm vivo during the 
maturation process. However, the insertion of a small number of precursor T 
cells in a matched BMT results in the complete replacement of ADA(+) T cells in 
the patient. Therefore, if the transferred ADA gene in a gene therapy protocol 
is expressed during T cell development, then these cells should indeed have a 
strong selective growth advantage. 
ADA deficiency, although rare, appears for these reasons to be an ideal 
Initial candidate for gene therapy. 
2. Describe the natural history and range of expression of the disease 
selected for treatment. What objective and/or quantitative measures 
of disease activity are available? In your view, are the usual 
effects of the disease predictable enough to allow for meaningful 
assessment of the results of gene therapy? 
SCID patients are generally agammagl obul inemic and fail to produce 
antibodies following immunization or infection. They also generally exhibit 
striking lymphopenia and are unable to mount T cell immune responses thereby 
making them susceptible to serious or fatal infections with opportunistic 
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Recombinant DNA Research, Volume 12 
