9.4.1 Potential Risks of Gene Transfer In Vivo 
Insertional mutagenesis . The possibility of causing malignancy 
in cells secondary to the random insertion of the DNA in the 
genome exists, though this risk is considered low (17-19). There 
is a remote chance that the vector could replicate in the host 
when FDA recommended procedures are not followed, and it is 
essential to screen all retroviral vector lots for replication- 
competent helper virus using the S + L” assay, testing -1/10 of 
each lot. When these guidelines have been followed in the past, 
there have been no complications detected in immunodef icient 
individuals. Two additional features of the study design 
provides additional safety features for this trial. All patients 
will be maintained on AZT, which exerts an anti-viral effect on 
murine retroviruses. Therefore, replication-competent viruses 
would be inhibited by this agent. Finally, the use of a less 
extended packaging sequence without gag should minimize the risk 
of recombination and the generation of replication-competent 
virus. With DNA microprojectile injection, the risk of an 
adverse event is even lower, since it cannot generate an 
infectious agent. In either case, blood samples will be obtained 
after treatment of each. PCR and S + L” assays will be performed 
to monitor for this unlikely event. In the case of biolistics, 
we would expect the risks to be similar or less than retroviral 
vectors, and related to the potential for insertional 
mutagenesis . 
The use of aminoglycoside antibiotics . The neomycin resistance 
gene, which encodes neomycin phosphotransferase (NPT) , 
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