Attachment- VI - Page 7 
2 . Preclimcal studies, including risk-assesanent studies 
Describe the experimental basis (derived fron tests m cultured 
cells and laboratory animals) for claims about the efficacy arri 
safety of the proposed system for gene delivery. 
a. Laboratory studies of the delivery system 
(1) What cells are the intended recipients of gene therapy? 
If recipient cells are to be treated in vitro and returned 
to the patient, hew will the cells be characterized before 
and after treatment? Vhat is the theoretical and practical 
basis for assuming that only the treated cells will act as 
recipients? 
(2) Is the delivery systan efficient in the sense that it 
results in the insertion of the desired unrearranged DMA 
sequences into the target cells of the patient. 
(3) How is the structure of the added DNA sequences monitored 
and what is the sensitivity of the analysis? Is the added 
DNA extrachrcmoscmal or integrated? 
(4) How many copied are inserted per cell? How stable is the 
inserted DN^ both in terms of its continued presence and 
its structural stability? 
b. Laboratory studies of gene expression 
Is the inserted gene expressed? TO what extent is expression 
only from the desired gene (and not from the surrounding DNA)? 
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