Recombinant DNA Advisory Committee - 03/1-2/93 
The members of the RAC continued to make minor modifications to the Procedures for 
Expedited Review and the Cover Sheet for Expedited Review. Dr. Walters suggested that a 
revised version of these two documents should be presented for final approval later on in 
the agenda. 
Before presenting the next agenda item. Dr. Walters suggested that the RAC should 
form a working group to analyze and develop different categories for the classification of 
human gene transfer and therapy protocols. The purpose for this exercise is to assist the 
RAC in developing certain categories of protocols that may be eligible for decentralized 
review. 
XII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A PHASE I STUDY OF GENE THERAPY 
OF CYSTIC FIBROSIS UTILIZING A REPLICATION DEFICIENT RECOMBINANT 
ADENOVIRUS VECTOR TO DELIVER THE HUMAN CYSTIC FIBROSIS 
TRANSMEMBRANE CONDUCTANCE REGULATOR cDNA TO THE AIRWAYS /DRS. 
WILMOTT, WHITSETT, AND TRAPNELL 
Review-Ms. Grossman 
Dr. Walters called on Ms. Grossman to present her primary review of the protocol 
submitted by Drs. Robert W. Wilmott and Jeffrey Whitsett of Children's Hospital 
Medical Center, Cincinnati, Ohio, and Dr. Bruce Trapnell of GTI, Gaithersburg, 
Maryland. 
Ms. Grossman provided a brief overview the proposed study. This protocol is a Phase I 
study to assess the safety and biological efficacy of a recombinant adenovirus delivered 
to the nose and lungs of patients with cystic fibrosis (CF). The investigators proposed to 
treat a total of 15 adult patients, who will be divided into 3 groups of 5 patients. Each 
group of patients will receive 1 x 10 10 , 1 x 10 11 , or 1 x 10 12 plaque forming units (pfu) of 
recombinant adenovirus. 
This protocol is more complex than the other CF protocols that have previously been 
reviewed by the RAC. This study involves the administration of vector to the nose and 
lung of the patients, followed by subsequent challenge with an equivalent dose of virus 2 
months after the initial treatment. The proposed vector is an El and E3-deleted type 5 
adenovirus. The cystic fibrosis transmembrane conductance regulator (CFTR) cDNA is 
expressed from a Rous sarcoma virus (RSV) promoter. 
Ms. Grossman said that the investigators responded to the majority of her written 
comments; however, there is still one remaining question regarding the sequencing of the 
vector. The investigators indicate that they will confirm the sequence of the viral 
Recombinant DNA Research, Volume 17 
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