Recombinant DNA Advisory Committee - 12/2-3/93 
degree of difficulty that might be encountered when administering this material 
throughout the tracheobronchial tree? 
Review-Dr. Secundy 
Dr. Secundy stated the following concerns about the Informed Consent document. This 
document states that patients should not become pregnant; however, an adequate 
explanation about the possible risks has not been provided. Due to the duration of this 
disease, CF patients may be more likely to become pregnant than other terminally ill 
patients; therefore, pregnancy is an important issue. If a patient becomes pregnant and 
withdraws from the study, who will provide patient follow-up? 
Other Comments 
Ms. Grossman commented on the technical problems of measuring the potentiometric 
differences between the treated nostril and the control nostril. This problem has not 
been adequately addressed by the investigators. Dr. Parkman asked about the 
recommended period for contraception since the risk of germ line gene insertion is 
unknown. Dr. Miller responded that there is minimal risk of germ line integration with 
local administration; therefore, contraception should not be required. Dr. Miller 
explained that the 44 amino acid coding sequence of the SV40 small T antigen at the 
polyadenylation site of the vector construct is unlikely to encode a gene product with 
transforming activity. Since the plasmid vector is not a virus, there is very little risk of 
replication and transmission to other individuals. 
Investigator Response-Dr. Sorscher 
Dr. Sorscher presented a diagram of the vector construct demonstrating that the small 
region of SV40 T antigen has been removed from the modified DNA construct. 
In response to the RAC's concerns about the ability to measure nasal bioelectric 
potential differences, the proposed techniques yielded consistent measurements. This 
procedure involves minimal discomfort to the patients. Consistently, 2- to 3-fold 
differences have been detected between the nostrils of CF patients and normal 
individuals. Therefore, correction of the CFTR defect should be measurable. Dr. 
Krogstad suggested that fluorescein could be used as a marker to monitor the amount of 
material that crosses to the other nostril by ciliary activity. 
With regard to the issue of contraception. Dr. Sorscher said the risk of germ line 
integration is very small since this construct is not a viral vector; however, the risk will be 
clearly stated in the Informed Consent document. Since the risk is minimal, the 
contraception requirement will be deleted. 
Dr. Miller asked whether inclusion of the ampicillin-resistance gene in the vector 
construct could compromise the treatment of pneumonia in CF patients? Dr. Sorscher 
responded that there are many other more useful antibiotics available. Ampicillin is not 
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Recombinant DNA Research, Volume 18 
