I. Description of Proposal 
A. Objectives and rationale of the proposed research 
State concisely the overall objectives and rationale of the proposed 
study. 
Severe combined immune deficiency (SCID) is the most profound of the 
primary immune deficiency diseases. It Is characterized by a dual system 
immune defect with virtual absence of all T and B cell Immune function. By its 
nature. SCID is a disease of infancy with most affected individuals dying of 
infection by two years of age. In about 1/4 of all SCID cases, deficiency of 
the purine catabolic enzyme adenosine deaminase (ADA) has been found. We 
propose to treat patients with ADA-deficient SCID (ADA(-)SCID) by inserting 
the human gene for ADA into the patient's bone marrow utilizing a retroviral 
gene transfer/autologous bone marrow transplantation system. 
Please provide Information on the following specific points: 
1. Why Is the disease selected for treatment by means of gene therapy a 
good candidate for such treatment? 
ADA(-)SCID is a good candidate disease for gene therapy for several 
reasons. It is an invariably fatal disease If untreated. Treatment of ADA 
deficiency by transplantation with bone marrow from an HLA-ldentical sibling 
donor results in the correction of the defective Immune system In these 
patients; however, only 1/3 of patients have a matched donor. Further. ADA 
deficiency has no major non-immunol ogic features which need correction or which 
cannot be corrected by bone marrow transplantation. Thus, successful insertion 
of a functioning ADA gene into the patient's own bone marrow cells should be 
sufficient to correct all clinically significant manifestations of the disease. 
The results of bone marrow transplantation also suggest that correction of the 
[6] Recombinant DNA Research, Volume 12 
