life of some ADA-deficient patients. This may be due to progressive loss of T 
cell precursors. It has been suggested that this may in part be due to some 
protective detoxification of deoxyadenosine by the maternal circulation while 
in utero . Newborns with ADA deficiency are more likely to have a pool of such 
T cell precursors. Additionally, they may have bone marrow stem cells which 
are more mitotically active and thus may be more infectable by retroviral 
vectors. Technically, an infant's smaller body mass would make the logistics 
of gene transfer easier in that a smaller number of cells would be treated; 
therefore, a smaller amount of virus would be needed. However, if cytoablation 
is required to enhance engraftment of treated cells, neonates would be at 
increased risk of morbidity (such as growth and neurodevel opmental retardation) 
compared to older children. 
b) Onset of SCID in infancy is the most common presentation of ADA 
deficiency. Thus, patients from this group would be the most available as 
subjects. Because these patients would have been identified by their frequent 
severe infections, they are less likely to benefit from gene therapy if there 
is a substantial delay from time of treatment to the development of immunity. 
However, these patients will also be more prone to toxicity from cytoablative 
therapy because several target organs such as the lung and liver may be 
compromised from previous infections. Therefore, gene therapy may be safer 
than high-risk cytoablation in these patients. 
c) Finally, we are aware of at least two children with ADA-deficiency and 
SCID who. at present, have survived to 11 and 13 years of age. Both have had 
multiple opportunistic infections. Lymphocyte lines from these two patients, 
established in our laboratory, show that they have approximately 8 and 2% of 
normal ADA activity. This is definitely more than found in a number of 
ADA-deficient SCID patients with onset of severe infections in infancy and 
F 74 ] Recombinant DNA Research, Volume 12 
