Recombinant DNA Advisory Committee- 9/12-13/94 
very issue needed to be discussed further. The investigator indicated that recipients of 
AAV-CFTR are still shedding the virus several days after administration. The 
decontamination procedure is not articulated. Dr. Straus said that these procedures 
should be discussed in terms of their effectiveness and practicality. Overall, Dr. Straus 
expressed his satisfaction of the well written protocol. 
Review-Dr. Dronamraju 
Dr. Dronamraju was satisfied with the written response by the investigator regarding the 
question of transduction rate and vector expression. The concern about virus shedding 
was not mentioned in the Informed Consent document, and it is unclear why patients 
should be advised not to talk to the reporters about their participation in the study. Dr. 
Dronamraju asked the investigator to elaborate on the toxicity study in primates. 
Other Comments 
Dr. Miller indicated that he would abstain from voting on this protocol since he is 
associated with a company involved in a part of this study. 
Dr. Parkman said this protocol employs a new vector system to treat CF. Since the RAC 
has approved several protocols using adenovirus vectors, it would be informative to the 
RAC to have investigators of those adenovirus protocols to offer a comparative 
assessment as to the pros and cons of these vector systems. He asked if animal studies 
are available in which these two vector systems have been compared in parallel. Dr. Doi 
asked the investigator to elaborate on the question of immunological responses to the 
administration of the AAV vector. Dr. Parkman noted immunological responses will be 
particularly pertinent to repeated vector administration. Mr. Capron asked how a subject 
would be treated if he or she withdrew from the study while still shedding the virus. 
Investigator Response-Dr. Flotte 
Dr. Flotte presented animal data to address the question of vector shedding. After 
administration of 10 11 AAV-CFTR particles to the right lower lung of a monkey, there 
were no detectable vector sequences from day 3 to day 21. The vector assay involved a 
PCR using a lysate of 293 cells co-cultured with nasal or bronchial fluid from the infected 
monkey in the presence of both adenovirus helper and wild-type AAV. The assay has a 
sensitivity of detecting 10 infectious units of AAV-CFTR present in these samples. The 
dose of AAV-CFTR used in this experiment is 10 times higher than the highest dose 
proposed for the human study. 
Responding to the question of decontamination. Dr. Flotte said that in the unlikely event 
if a patient is discharged while still shedding the vector, the patient will be instructed to 
decontaminate his/her nasal secretions and sputum with a 1% bleach solution. According 
to a study performed at Targeted Genetics, Inc. (Seattle, Washington), such a bleach 
solution will totally inactivate any wild-type AAV. Dr. Flotte welcomed suggestions from 
RAC members as to how to address this problem keeping in mind patient’s overall 
Recombinant DNA Research, Volume 20 
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