Attachment VI- Page 5 
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disease predictable enough to allow for meaningful assessment of 
the results of gene therapy? 
3. Is the protocol designed to prevent all manifestations of the disease, 
to halt the progression of the disease after symptoms have begin 
to appear, or to reverse manifestations of the disease in seriously 
ill victims? 
4. vfriat alternative therapies exist? In what groups of patients are 
these therapies effective? Vhat are their relative advantages and 
disadvantages as compared with the preposed gene therapy? 
B. Research design, anticipated risks and benefits 
1 . Structure and characteristics of the biological system 
Provide a full description of the methods and reagents to be employed 
for gene delivery and the rationale for their use. The following 
are specific points to be addressed: 
a. What is the structure of the cloned CNA that will be used? 
(1) Describe the gene (genarruc or cDf^A) , the bacterial plasmid 
or phage vector, and the delivery vector (if any). Provide 
complete sequence analysis or a detailed restriction map of 
the total construct. 
(2) v-hat regulatory elements does the construct contain ( e.g . , 
promoters , enhancers, polyadenylation sites, replication 
origins, etc.'? 
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