Recombinant DNA Advisory Committee- 9/12-13/94 
Committee Motion 
Dr. DeLeon made a motion to approve the protocol on the contingency that Dr. Crystal 
would remove the quantitative PCR assay from the protocol. Dr. Crystal agreed to this 
stipulation. Dr. Parkman added a friendly amendment to ask the investigator to provide 
the toxicology data from the cotton rat experiments. Dr. Crystal said this is a completed 
study. 
Ms. Meyers said that she will abstain from voting because of the conflicting statements 
from the ad hoc expert and the investigator. Dr. Walters noted that Dr. Ross abstained 
due to her employment by Cornell University. 
The RAC approved a motion made by Dr. DeLeon and seconded by Dr. Parkman to 
accept the protocol submitted by Dr. Ronald G. Crystal of New York Hospital-Comell 
Medical Center, New York, New York, by a vote of 12 in favor, 1 opposed, and 2 
abstentions. Approval of the protocol is contingent on review and approval of the 
following by the primary RAC reviewers: (1) removal of the quantitative PCR assay from 
the study, and (2) toxicology data derived from cotton rat experiments (> 6 doses of 
adenovirus vector) obtained at 1 week and 1 month post vector administration. 
Summary 
Dr. Ronald G. Crystal of New York Hospital-Comell Medical Center, New York, New 
York, may conduct gene transfer experiments on 26 patients (> 15 years of age) with CF. 
A replication deficient recombinant adenovirus vector will be used to transduce the 
human CFTR gene to the epithelium of large bronchi. The vector to be used, 
Ad o% CFTR.10, is an E1E3" adenovirus-5 based vector with an expression cassette in the 
El region that includes the CMV promoter. The study will initially define the safety and 
kinetics of expression of the normal CFTR cDNA in the airway epithelium following 
single dose administration of ascending doses to the airways in different individuals. Once 
the dose schedules are defined, it will evaluate repeat administration on these individuals. 
Differences from Protocol #9212-034 are: (1) administration of vector to more localized 
areas of airways, (2) more careful definition of pharmacodynamics of CFTR expression, 
(3) evaluation of CFTR expression following repeat administration, and (4) use of a more 
active promoter/enhancer in the expression cassette. 
X. AMENDMENTS TO SECTIONS I, III, TV, V AND APPENDIX M OF THE NIH 
GUIDELINES REGARDING NIH AND FDA CONSOLIDATED REVIEW OF HUMAN 
GENE TRANSFER PROTOCOLS/DRS. WIVEL AND NOGUCHI 
Dr. Walters mentioned that several written comments were submitted in response to the 
proposal of NIH/FDA consolidated review. Included in the meeting materials are a letter 
dated September 7, 1994 from Ms. Wendy L. McGoodwin, Acting Executive Director of 
Council for Responsible Genetics, Cambridge, Massachusetts, and a letter dated 
September 12, 1994, from Mr. Jeremy Rifkin, President, and Mr. Theodore Waugh, Staff 
Attorney of the Foundation on Economic Trends, Washington, D.C.. 
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Recombinant DNA Research, Volume 20 
