(4) How many copies are present per cell? How stable is the 
added DMA both in terns 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 added DN^ occur? 
Is the product biologically active? Vfriat 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) What 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 
viral sequences is likely to occur in the patient's 
cells? Vhat steps have been taken in designing the 
vector to minimize instability or variation? What 
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Recombinant DNA Research, Volume 1 1 
