Attachment II - Pg. 7 
(3) Safety. 
What risks are associated with the del i very /expression system? 
(a) If a retroviral system is used: 
[1] Are there any infectious particles produced in any cell type 
treated with the retroviral vector preparation? 
[2] How stable is the retroviral vector and the resulting provi- 
rus to loss, rearrangement, recombination, or mutation? How 
much rearrangement or recombination with endogenous or other 
viral sequences may occur in the patient's cells, either in 
culture or in the patient? What steps have been taken In 
designing the vector to minimize Instability or variation? 
[3] Could there be any harmful effects from the treatment: 
i.e., malignancy, harmful mutations, regeneration of infec- 
tious particles, immune responses. How would harmful ef- 
fects be monitored and what Is the sensitivity? What steps 
have been taken in designing the vector to minimize patho- 
genicity? 
[4] Is there evidence from animal studies that vector DNA has 
gotten Into any other tissue besides the cells treated, spe- 
cifically germline cells? What is the sensitivity of analy- 
sis? 
[5] Has a protocol similar to the one proposed for a clinical 
trial been carried out in primates? With what results? 
(b) If a non-retrovl ral delivery system is used: what animal stud- 
ies have been done to determine if there are pathological or 
other undesirable consequences of the protocol (including Inser- 
tion of DNA Into cells other than those treated)? What are the 
tests to be used and their sensitivity? 
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