Recombinant DNA Advisory Committee- 9/12-13/94 
In regard to the question why the vector was detected in liver after administration to the 
lung of a monkey, Dr. Flotte said that the vector was not detected in other parts of the 
gastrointestinal system. He speculated that in this particular instance, the vector might 
have spread to liver through the blood circulation. Since hepatocytes normally express the 
CFTR gene, no adverse effects will be expected. 
Responding to a question on the comparative merit of AAV versus adenovirus vectors, Dr. 
Flotte said that the main impetus for pursuing CF gene therapy with the AAV vector was 
its ability for persistence in infected cells and for long-term expression. AAV-CFTR can 
function as an episome and integrates at lower frequency than wild-type AAV but is still 
capable of long-term persistence. Since the AAV vector does not contain any viral coding 
sequences, it avoids the problem of inflammatory effects caused by expression of viral 
proteins of the adenovirus vectors. 
Committee Motion 
Dr. Straus made a motion to approve the protocol with several contingencies. Dr. Smith 
asked for a clarification about the contingency of virus shedding. Dr. Straus said that the 
investigator is permitted to proceed with the study cohort by cohort. If the subjects are 
still shedding virus 7 to 10 days after vector administration, the subjects will be permitted 
to go home with instructions about the decontamination procedure. In addition, the 
family members should be asked for consent to be screened for the presence of vector. 
The recruitment for other cohort studies will be discontinued until the RAC makes further 
recommendations to proceed with the study. 
A friendly amendment, as suggested by Mr. Capron, was added to the motion for 
approval. This amendment requests a revision of the Informed Consent document with 
regard to patient withdrawal. Dr. D. Ginsburg seconded the motion. 
With regard to the statement in the Informed Consent about communication with the 
newspaper or television reporters, Dr. Flotte said that the statement is to alert the patients 
about the possibility of publicity. 
The RAC approved a motion made by Dr. Straus and seconded by Dr. D. Ginsburg to 
accept the protocol submitted by Dr. Terence R. Flotte of the Johns Hopkins Children’s 
Center, Baltimore, Maryland, by a vote of 16 in favor, 0 opposed, and 1 abstention. The 
RAC approval is contingent on review and approval of the following by the RAC primary 
reviewers: (1) Submit a revised protocol that explains that each cohort will be evaluated 
for virus shedding. If virus shedding is detected at > 10 days post-vector administration, 
vector administration to subsequent cohorts is prohibited. Any subject in whom virus 
shedding has been detected > 10 days post-vector administration will be released from the 
hospital; however, family members and close contacts will be informed of the possibility 
that they may be screened for the virus. The RAC recommended that if a subject is 
released from the hospital while actively shedding virus, family members and close 
contacts should be evaluated for the presence of the vector. (2) Submit a revised 
Informed Consent document incorporating a statement that informs subjects that in the 
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Recombinant DNA Research, Volume 20 
