treadmill, etc.) during this time period, either in the patient’s room or 
another approved isolation site. 
Potential benefits: 
Patients are not expected to benefit directly from this study. The correction 
of epithelial function in a small area of the nose is not likely to affect overall clinical 
outcome. However, the information generated from this study is likely to benefit 
the CF patient population at large. Information will be crucial for the design of 
studies for delivery of gene therapy to the lower airways, and the successful 
development of genetic approaches to the treatment of human disease has potential 
benefit to CF patients and greater mankind. 
On balance, the risks to the study subjects would seem to be small in view of 
the overall safety of the recombinant vector, the general study design involving a 
dose-escalation, and the use of the nasal epithelium for the initial pilot studies. The 
risk/benefit ratio for this study would appear justified in terms of overall advances 
in medical knowledge for this particular patient population. 
VI. PRODUCTION OF CFTR ADENOVIRUS 
A critical part of the safety aspects of this protocol relates to the quality 
control and quality assurance associated with recombinant virus production. It is 
critical to demonstrate that the recombinant virus can be reproducibly 
manufactured in a way that the final product is of sufficient therapeutic quality and 
free of replication competent virus or other adventitious agents. 
Virus production is performed in a BL2+ facility at the University at 
Michigan that is solely dedicated to production of recombinant adenoviruses. A 
schematic of the laboratory is provided in Appendix L. Within this laboratory there 
is a 4 ft laminar flow hood and double stack incubator that is dedicated to the 
production of Ad5-CB-CFTR. The detailed standard operating procedures for 
producing virus are described below as is the strategy for assuring quality of the final 
product. 
Recombinant DNA Research, Volume 17 
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