criteria, including a positive sweat chloride test. 
(2) The CF genotype will be identified. 
(3) The CF genotype will be either "delta F508" homozygotes or the "delta 
F508" mutation on one allele and on the second allele, a null mutation 
known not to produce CFTR mRNA (i.e., a delta F508-null compound 
heterozygote at the mRNA level) . The purpose of this genotype 
restriction is for technical convenience based on the goal of 
demonstrating that the administration of AdCFTR in vivo will change 
the genotype of the respiratory epithelium at the mRNA level (using 
sequence analysis and PCR with specific probes; see Section 5. 5. 3.1). 
With this genotype restriction, the sequence and specific probe 
analyses will be definitive pre- therapy and after correction. 
Ability to Give Informed Consent 
Constraints 
(1) The protocol is complex, with major implications for the study 
population in regards to risk/benefit considerations, and decisions 
of the study population in regards to the implications of personal 
freedoms imposed by the AdCFTR experiment treatment period (see 
sections 5.6.2 - 5.6.4). 
Constraints Regarding Design of The Protocol 
(1) All patients must be 21 years or older. 
Protection from Germ Line Gene Transfer 
Constraints 
(1) The target for gene therapy for this protocol is the respiratory 
epithelium of the airways. Studies are ongoing in cotton rats and non- 
human primates to demonstrate that there is no transfer to other 
organs (including gonads) when the vector is administered by the 
respiratory route. However, as it is not possible to develop absolute 
evidence that germ line transfer will not occur when a vector is 
administered in vivo by the respiratory route, the protocol should be 
carried out in individuals that have definitive evidence of being 
incapable of bearing offspring. Relevant to this consideration is that 
almost all males with CF are sterile (Stern et al . , 1982; Boat et al . , 
1989) . 
Conclusions Regarding Design of the Protocol 
(1) As inclusion criteria to enter the vehicle control period (see section 
5.6.3) and AdCFTR experimental treatment period (see 5.6.4), studies 
in the baseline period (see 5.6.3) must document sterility in males 
Recombinant DNA Research, Volume 16 
[737] 
