Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Motulsky inquired if there is any coordination between the different laboratories that 
are conducting gene transfer research for the treatment of CF. Dr. Wilson responded 
that through the CF Foundation, there is substantial networking. The CF Foundation 
supports scientific meetings for the exchange of current information and data in the area 
of gene therapy. 
Dr. Post asked Dr. Trapnell if the CFTR cDNA has been sequenced for the GTI 
supplied adenovirus vector. Dr. Trapnell answered that the plasmid was sequenced and 
found to be different from the sequence published in Science. However, Dr. Lap-Chi 
Tsui's laboratory said that transcriptional errors had been found, and that the sequence 
published in Science was not entirely correct. The Science paper had transcriptional 
errors that have since been corrected. The sequence derived at by GTI is the same as 
the final sequence obtained by Dr. Tsui's laboratory. 
Dr. Post asked Dr. Wilson if he compared his CFTR cDNA sequence to the sequence 
published in Science. Dr. Wilson explained that he compared the sequence to the one in 
GenBank. Dr. Parkman said that the CF Foundation should identify the correct 
sequence of CFTR cDNA. Dr. Wilson stated that he will cross-check the sequence 
against Dr. Tsui's corrected sequence. 
Dr. Straus stated that the RAC should be cognizant of the duplication of trials. Not only 
are these trials expensive, but they require a minimum number of subjects per trial. 
Each trial encompasses a certain degree of risk. With approval of 5 similar trials, these 
risks are encumbered at 5 centers. Although this approach may be exciting, it may 
ultimately prove to be non-therapeutic. Therefore, the RAC should emphasize the 
importance of animal models in assessing the safety of vectors. Dr. Boucher noted that 
the proposed study is a safety trial. 
In regard to the question of over-expression. Dr. Boucher explained that a number of 
studies had been conducted in which CFTR was over-expressed in human epithelial 
sheets that were polarized. Data demonstrates that there is a level of saturation in the 
apical membrane. No evidence of expression in the contralateral membrane has been 
observed. CFTR seems to target in appropriate amounts. Dr. Boucher introduced his 
collaborator Dr. Knowles to respond to questions about the informed consent document. 
Presentation-Dr. Knowles 
Dr. Knowles addressed the issue of holding patients in quarantine. The IRB, the 
Institutional Biosafety Committee (IBC), and local health officials are in agreement that 
patients should be confined for 3 days to protect the public welfare. This statement will 
be included to inform patients that they will not gain any direct benefit from this 
particular protocol. 
Recombinant DNA Research, Volume 17 
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