Attachment VI - Page 8 
10 
In vhat percentage of cells does expression occur? Is the 
product biologically active? What percentage of normal activity 
results frcm 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 arty, 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? What steps have been taken m designing the 
vector to minimize instability or variation? What 
laboratory studies have been performed to check for 
stability, and what is the sensitivity of the analyses? 
(c) What laboratory evidence is available concerning poten- 
tial harmful effects of the treatment, e.g., malignancy, 
harmful mutations, regeneration of infectious particles, 
or lnrmne responses? What steps have been taken in 
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