Recombinant DNA Advisory Committee - 12/3-4/92 
Dr. Walters noted that the informed consent document states, Participation in this study 
does not mean automatic inclusion in subsequent studies. Would an individual who 
participates in this protocol be less eligible for participation in later studies? Dr. Crystal 
stated that participation in this protocol would not affect participation in subsequent 
protocols. Dr. Walters also asked if aerosol administration of vector would be more 
comfortable to the patient than bronchial lavage. Dr. Crystal responded that 
adenoviruses can certainly be aerosolized; however, an unnecessary safety risk may be 
introduced particularly to the health care workers. Aerosol administration may be 
proposed for future protocols, but it is not an appropriate choice for this early study. 
Dr. Zallen asked if health care workers would be monitored in any way. Dr. Crystal said 
that there are no plans to monitor the health care workers. This decision is based on 
recommendations from both epidemiologists and hospital consultants. 
Dr. D. Miller asked if reconstruction experiments were performed to demonstrate that 1 
in 10 particles of adenovirus are detectable. Dr. Crystal said that these experiments have 
been performed. In vitro assays will be performed on normal allogeneic human airway 
epithelium in addition to their own airway epithelium at an MOI that is 5 times the 
maximum dose. If 200 wild-type adenovirus particles are distributed among 10 10 cells, 
the actual MOI is approximately 10 5 . Dr. D. Miller asked if a CF patient were to obtain 
100 particles of replication-competent adenovirus, what complications would be 
observed? Dr. Ginsberg said that 100 particles instilled into a CF patient could 
theoretically produce disease. 
Dr. Schaechter asked what percentage of the patient's lung would have to become 
transfected in order to realize a therapeutic benefit. Dr. Crystal explained that the gene 
product is expressed at extraordinarily low levels. Very little expression is required to 
improve health. The mRNA expression in the airway surface cells is probably due to 
only 1 or 2 copies. This number may be somewhat higher for mucosal cells. Dr. Chu 
has demonstrated that exon 9 is a critical exon in the first nucleotide binding fold. Dr. 
Chu determined that the 3 CF patients studied who exhibited a 90% reduction in exon 9 
were completely normal. This data suggests that all the patient's cells do not have to 
have the normal CFTR gene. Data from Dr. Richard Bouchet's laboratory suggests that 
a 7 to 10% transduction of the epithelial sheet is all that is required to correct the 
biology of these cells. Dr. Crystal suggested that cell-to-cell communication is a possible 
explanation for this result. 
Ms. Meyers suggested that the investigators should add a paragraph regarding protection 
of the patient from the media. Dr. Crystal agreed to add a section regarding protection 
from the press to the informed consent document. 
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Recombinant DNA Research, Volume 16 
