Recombinant DNA Advisory Committee - 12/3-4/92 
in the protocol after they have received financial compensation? Dr. Zallen commended 
the investigators for other aspects of the recruitment process, i.e., visiting patients, their 
families, and private physicians during the initial screening process. Dr. Zallen said that 
she would like the opportunity to review the revised informed consent document. 
The Points to Consider document is somewhat flawed because there are numerous 
references to the protocol. The document does not stand alone as an informational 
source. The RAC should establish whether this format is acceptable. The non-technical 
abstract is too brief; more information should be included regarding the experimental 
procedures. 
Other Comments 
Dr. Walters noted that the expected benefits section of the informed consent document 
clearly states that the patient will not benefit from this study; however, this assertion 
should be clearly stated in the purpose of the research section, which is in the first part 
of the document. 
Dr. Parkman said that patients will be isolated in a negative pressure room for 10 days. 
If their cultures are negative, they will be released. How many cultures will be 
performed? If the patients continue to shed virus for longer than 10 days, how many 
times will they have to be negative before they can leave isolation? What are the 
exclusion criteria if a patient develops a viral infection in the period immediately prior to 
transduction? What are the exclusion criteria if a patient has Ela sequences in the 
bronchi at the time of treatment? 
Presentation-Dr. Wilson 
Dr. Wilson explained that an attempt was made to localize the product of the CFTR 
gene in the proximal airway using in situ hybridization and immunocytochemistry. The 
CFTR gene was difficult to detect in the surface epithelium of the proximal airways. 
However, CFTR is extensively expressed throughout the distal airway as well as the 
alveolar structures. These data suggest that the cellular targets of this therapy are quite 
numerous and diverse-starting with the proximal airway and submucosal areas and 
throughout the distal airway and airspace. An attempt will be made to selectively block 
a segment of the lung so that the efficiency of gene transfer can be determined in the 
bronchus, bronchioles, and the distal airway. 
The animal model used to generate the in vivo data is the CF mouse, which was 
developed by Dr. John Engelhardt. This model takes advantage of the ability to grow 
human epithelial cells in a immune-deficient mouse. Bronchial epithelial cells are 
removed from a human CF lung and transplanted to the trachea of a rat that has been 
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