Recombinant DNA Advisory Committee - 12/3-4/92 
properties and transport properties. Specifically, the nasal epithelial cells of these 
patients have the same chloride transport defect as the bronchial epithelia. The nasal 
epithelium has been used traditionally for the initial testing of therapies designed to treat 
CF. The nasal epithelium offers the following advantages for assessing safety and 
efficacy: (1) there is a defined area of application, (2) information can be derived 
regarding the relationship between the input of virus and the biological response in order 
to determine the optimal MOI, (3) nasal administration offers the advantage of frequent 
measurements because it is a non-invasive procedure, (4) daily measurements can be 
determined without risk to the patient, (5) surface fluid can be obtained for the purpose 
of culturing for virus, and cells can be monitored for possible inflammatory responses, 
(6) biopsies can be obtained from the nasal epithelium, which will be important for the 
assessment of cytopathic effects and the detection of subtle changes in the epithelium, 
(7) cell function can be monitored by the measurement of trans-epithelial voltage across 
the nasal epithelium, and (8) nasal administration will allow for the determination of 
treatment-related versus procedure-related adverse consequences. 
Dr. Welsh responded to Dr. Parkman's concern regarding patient cultures for the 
determination of virus excretion and secretion. Dr. Welsh stated that cultures will be 
performed on the nose, pharynx, blood, urine, and stools. Adenovirus antibody 
production will be monitored as well as cell analysis for the assessment of inflammation 
and cytopathic effects. 
Dr. Welsh explained that the most important goal of the protocol will be to assess 
efficacy, i.e., will CFTR correct the chloride channel defect in these patients? Efficacy 
will be assessed by the trans-epithelial electrical potential differences observed across the 
nasal epithelium. This technique was originally developed by Drs. Michael Knowles and 
Richard Bouchet. Also, mRNA and protein will be monitored. 
Patients will be greater than 18 years of age, male or female, genotypically defined, have 
mild or moderate lung disease, and be seropositive for adenovirus. Exclusion criteria 
include clinical instability, upper respiratory infection, and virus shedding. 
The original protocol proposed that the nasal epithelium should be demonstrated to be 
positive for El genes. Considering the comments offered by Dr. Ginsberg during Drs. 
Crystal and Wilson's protocols and the sense of the RAC, Dr. Welsh asked that this 
requirement be deleted from the protocol. 
The proposed vector is an El deleted Type 2 adenovirus that encodes for CFTR. This 
vector has an Ela promoter that retains the E3 region. This virus is impaired because of 
its substantial length. 
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Recombinant DNA Research, Volume 16 
