Monkey Safety Protocol (P3 Containment) 
AMENDMENT TO ANIMAL RESEARCH PROTOCOL » 4-CH-l 
A) Brief description Including purpose, experimental design and animal 
selection. 
The purpose of this study Is to determine the safety of amphotroplcal ly 
packaged murine retroviral vectors administered to primates. 
Current strategies for human gene therapy require the exposure of human 
bone marrow cells to recombinant retroviruses. To assess the hazards of 
exposing human cells to these retroviral vectors, we propose to inject a large 
quantity of the replication defective amphotroplc SAX vector Intravenously Into 
primates. (The SAX vector contains a neomycin resistance gene and a SV40 
promoted human adenosine deaminase gene within the LTR regions of the Moloney 
Murine Leukemia Virus). Since the recombinant retroviral vectors that will be 
used for human gene therapy may be contaminated with replication competent 
helper virus, we also plan to Inject a high dose of wild-type amphotroplc 
helper virus (4070A) intravenously and monitor for adverse effects. 
Adverse effects to be monitored are (1) viremia. by S + /L~ assay of plasma 
(2) infection, by assaying tissues such as bone marrow for evidence of the 
provirus and vector/viral expression (3) recombination, by performing DNA 
analysis on any virus Isolated (4) long term complications (e.g.. malignancy). 
B) Retroviral vector preparations to be administered: 
Animal 1 - Inject 10 ml /kg (approximately 40 ml) of S3A supernate 
(amphotropical ly packaged SAX vector with a titer of 2 x 10^ and 
3 
contaminating helper virus with a titer of approximately 2 x 10 ). 
Animal 2 - Inject 8 ml /kg of S3A supernate with 2 ml /kg of amphotroplc wild 
type virus 4070A. 
Animal 3 - Inject 10 ml /kg of 4070A. 
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Recombinant DNA Research, Volume 12 
