DNA extrachromosomal or integrated? Is the added DNA 
un rearranged? 
(4) How many copies are present per oell? How stable is the 
added Dt& both in terms of its continued presence and its 
structural stability? 
b. Laboratory studies of gene expression 
Is the added gene expressed? To what extent is expression 
only from the desired gene (and not from the surrounding DNA)? 
In what percentage of cells does expression from the added DNA 
occur? Is the product biologically active? What percentage of 
normal activity results from the inserted gene? Is the gene 
expressed in cells other than the target cells? If so, to 
what extent? 
c. Laboratory studies pertaining to the safety of the delivery/ 
expression system 
(1) If a retroviral system is used: 
(a) Wiat cell types have been infected with the retroviral 
vector preparation? Which cells, if any, produce 
infectious particles? 
(b) How stable are the retroviral vector and the resulting 
provirus against loss, rearrangement, recombination, or 
mutation? What information is available on how much 
rearrangement or recombination with endogenous or other 
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