Recombinant DNA Advisory Committee - 03/1-2/93 
antibodies in response to the modified adenovirus? Is there any possibility of 
homologous recombination which would result in a pathogenic virus. Is there any 
concern about over-expression of the CFTR gene? Is it legal to confine patients for up 
to 3 days if they are excreting virus if they do not want to be confined? Data 
demonstrates that the gene does not penetrate the submucosal glands. How important 
are these glands at restoring complete function? 
Review--Dr. Zallen 
Dr. Zallen explained that her initial written comments were regarding the source of the 
vector and the use of the term "gene therapy" in the informed consent document. The 
proposed vector will be supplied by investigators who are moving from the University of 
Michigan to the University of Pennsylvania. She inquired whether this transition would 
create any unforseen problems with regard to obtaining the vector. Also, the RAC 
should consider the appropriateness of the term "gene therapy" since this protocol is a 
Phase I study that has no therapeutic intent. 
The statement, "I am unlikely to gain any medical benefit from this study" should be 
revised to a stronger statement such as, "I will not get any benefit from the study." It is 
unlikely that transduction of a small portion of the nasal epithelium with the CFTR gene 
will result in any benefit to the patient's disease. 
The investigators' responses to the Points to Consider were not complete. The listing of 
the questions far exceeds the responses. The reader is prompted to refer to the protocol 
for most of the answers. The Points to Consider is a document that is read by a much 
larger audience than the RAC; therefore, the committee should encourage investigators 
to provide complete responses to the document. The RAC should begin to consider an 
issue that is not particular to this protocol. Specifically, the RAC should discuss whether 
a protocol that has been approved at one institution can be conducted at another 
institution. There may be a great deal of variability in the conditions between 
institutions. Dr. Walters agreed with Dr. Zallen that the RAC should begin discussion 
on this issue. 
Other Comments 
Ms. Meyers noted that the investigators have provided a model statement about a 
request for autopsy in the informed consent document. All investigators submitting 
human gene transfer protocols for review by the RAC should include a similar statement. 
Dr. Chase agreed with Dr. Zallen's comment about the use of the term "gene therapy." 
Dr. Leventhal suggested that "gene transfer" is acceptable alternative wording. This 
language has been adopted for other protocols. 
Recombinant DNA Research, Volume 17 
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