viral sequences is likely to occur in the patient’s 
cells? What steps have been taken in 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., development 
of neoplasia, harmful mutations, regeneration of 
infectious particles, or inmune responses? Vhat steps 
have been taken in designing the vector to minimize 
pathogenicity? Vhat laboratory studies have been 
performed to check for pathogenicity, and what is the 
sensitivity of the analyses? 
(d) Is there evidence frcm animal studies that vector CNA 
has entered untreated cells, particularly germ line 
cells? What is the sensitivity of the analyses? 
(e) Has a protocol similar to the one proposed for a clin- 
ical trial been carried out in non-human primates and/ 
or other animals? Wi at were the results? Specifically, 
is there any evidence that the retroviral vector has 
recombined with any endogenous or other viral sequences 
in the animals? 
(2) If a non-retrcviral delivery system is used: Vhat animal 
studies have been done to determine if there are Datholooical 
Recombinant DMA Research, Volume 1 1 
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