Recombinant DNA Advisory Committee - 06/7-8/93 
in the Informed Consent documents were outlined. Overall, the protocol is well thought 
out and promises to be successful. Dr. Motulsky recommended approval of the protocol 
with the inclusion of minor revisions. 
Review-Dr. Carmen 
Dr. Carmen stated that animal data demonstrated that bone marrow cell ablation is not 
a necessary predicator for correcting enzyme deficiency. The protocol will test this 
hypothesis in humans. The research design is lucid and carefully crafted. The Informed 
Consent document correctly emphasizes the gene "transfer" rather than the "therapy" 
features of the project. Dr. Carmen asked the PI to explain why Childrens Hospital of 
Los Angeles will perform transduction of bone marrow and the NIH will transduce 
peripheral blood cells. Why is the vector proposed for the human study different from 
the vector used in preclinical studies? Dr. Carmen recommended approval of the 
protocol. 
Investigator Response-Dr. Karlsson 
Responding to Dr. Haselkom's question regarding the choice of vector, Dr. Karlsson 
explained that GIGc was chosen as the vector because it produced the highest titers and 
levels of gene expression by macrophages in the murine model. When the MSG vector 
system became available later, no additional advantage was found. Since there is little 
human experience with CD34( + ) cell transduction and transplantation without 
myeloablation, a comparison will be made between bone marrow cells and peripheral 
blood cells. Five patients will receive transduced bone marrow cells, and 5 patients will 
receive transduced peripheral blood cells. Investigators at the NIH have extensive 
experience with peripheral blood cells, and investigators at the Childrens Hospital of Los 
Angeles possess expertise with ABM transplantation. If one cell source proves to be 
more efficacious than the other, the optimal source will be used by both institutions. 
Responding to Dr. Carmen’s comment about the choice of PA317/GlGc vector and 
packaging cell line, Dr. Karlsson stated that this packing cell line and vector is probably 
functionally equivalent to Dr. Barranger's packaging cell line and vector. The 
PA317/GlGc system is available and efficacious based on transduction and expression 
data in the target CD34( + ) cells. Dr. Kohn agreed with Dr. Karlsson's statement 
regarding the similarity between the two vectors. Ms. Meyers commented that the 
Informed Consent document is very well written. 
Committee Motion 
A motion was made by Dr. Motulsky and seconded by Dr. Haselkom to approve the 
protocol. The motion passed by a vote of 14 in favor, 0 opposed, and 4 abstentions. 
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Recombinant DNA Research, Volume 17 
