Recombinant DNA Advisory Committee- 9/12-13/94 
physical and psychological well-being. 
Dr. Flotte said that a patient’s used nasal tissues and sputum will be disposed in a bucket 
of bleach solution. Dr. Straus noted that this procedure will not prevent virus spreading 
by other routes such as aerosol created by coughing or hand to nose contact involving 
other individuals. Dr. Parkman expressed his concern about discharging patients who are 
actively secreting a vector. All RAC approved protocols require patient isolation until 
absence of virus shedding. 
Dr. Smith asked if there was virus shedding at sites other than the nose in the monkey 
experiment. Dr. Flotte said that samples have been collected from urine and stool but 
have not been tested for the presence of vector. 
Dr. Miller commented that there is little danger in spreading an AAV vector carrying the 
CFTR gene. Ninety percent of the human population already is infected with AAV as 
well as adenoviruses. AAV is nonpathogenic, and the vector is completely replication 
defective. There is little consequence of transducing a normal CFTR gene to other 
individuals since the gene is normally expressed. Dr. Parkman was concerned about the 
household contacts when the patients return to their home. The household members do 
not sign the Informed Consent document to have gene transfer from the research subjects. 
Dr. Miller said that this is the same argument advanced during the approval of other 
adenovirus CF protocols. Dr. Samulski said that there are published reports regarding 
cellular effects of CFTR being expressed in cells that do not normally express this protein. 
It is common sense to play it safe for the first trial of a new vector system. Dr. Chase 
remarked even if the AAV-CFTR is harmless, knowingly spreading the laboratory- 
produced virus to other individuals is a cause for concern to the general public. 
Dr. Flotte said it is unreasonable to isolate patients indefinitely if they continue to shed 
virus. It has to be balanced with the problem of patient recruitment and patient’s right to 
leave hospital if the patient withdraws from the trial. The contingency position is to give 
pertinent information to patients about how to decontaminate the virus. Considering 
there are no known adverse effects of spreading the vector, putting great burden on that 
particular virus-shedding patient would seem to be inappropriate. 
Ms. Meyers asked if it would be acceptable to amend the protocol to state that patients 
will be isolated until there is no shedding. Dr. Flotte agreed to this change, but Dr. 
French Anderson of University of Southern California raised the issue of prolonged 
shedding, i.e., for more than 6 months. Dr. Parkman said that there is a theoretical 
possibility that a patient would have to be discharged before shedding stops. Would 
household members be required to sign the Informed Consent document for this unlikely 
event? Dr. Samulski suggested that the experience of virus shedding from the trials of 
adenovirus vectors is a useful reference. In the case of AAV, the likelihood of generating 
productive infection is very small since it needs simultaneous infection with 3 viruses. 
Dr. Smith asked for clarification of two points: (1) the frequency of subject testing for 
virus shedding, and (2) the likelihood that subjects will return not only to home but will go 
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Recombinant DNA Research, Volume 20 
