(semen analysis) , and in females (the absence of a uterus and/or 
ovaries) . 
Necessity to Frequently Obtain Biologic Specimens From the Airways 
Constraint 
(1) To demonstrate biologic efficacy in the airways, it is necessary to 
frequently obtain biologic specimens by fiberoptic bronchoscopy, a 
procedure that requires informed consent and is associated with some 
morbidity (fevers, occasional infections) in individuals with CF. The 
procedure requires local anesthesia and is associated with some 
discomfort. Jn addition, the subject has to have lung function 
adequate to permit frequent bronchoscopy, and airways large enough to 
permit use of an adult bronchoscope (because of the diameter of the 
channels used for sampling) . 
Conclusion Regarding Design of the Protocol 
(1) All patients must have demonstrated ability to undergo the 
bronchoscopy and sampling procedures without difficulty. 
Recombination, Complementation and Environmental Concerns 
Constraints 
(1) AdCFTR is designed to be replication deficient in that it is Ela“ and 
(most of) Elb - and it does not replicate in freshly isolated human 
airway epithelial cells at levels that are detectable. However, 
addition to AdCFTR of the appropriate genetic information, either by 
recombination or by complementation in trans . may result in the 
production of more AdCFTR (by complementation) or a replication 
competent virus (by recombination) . 
(2) AdCFTR is an infectious agent, albeit designed to be replication 
incompetent. There is a theoretical risk to the environment for 
release of AdCFTR and/or a recombinant virus, mediated either from 
genetic information in the respiratory epithelium or from an exogenous 
viral source. 
Conclusions Regarding Design of the Protocol 
(1) Evaluate patients in the baseline period to ensure that they do not 
harbor an infectious virus relevant to the respiratory tract. 
(2) Evaluate the respiratory epithelium of patients prior to inclusion to 
insure that they do not harbor Ad5 DNA sequences for Ela, a region 
deleted in AdCFTR. 
(3) Prior to inclusion in the protocol, recover airway epithelial cells 
from individuals with CF, infect with AdCFTR and demonstrate that the 
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Recombinant DNA Research, Volume 16 
