7.3 Vehicle and Vector Administration 
Protocol Schematic Flow Diagram 
Event 
Time 
Admission Day -4 
Viral Cultures 
Baseline Studies 
Vehicle Administration 
▼ 
Vector Administration 
(If Viral Culture Negative) 
T 
Evaluation 
I 
Evaluation 
Viral Cultures 
Day 0 
Day 3 
Day 10 
t 
Discharge 
Day 14 
Patients will be studied on the day of admission (day -4) to provide baseline data. 
Fiberoptic bronchoscopy will be performed on the day of admission for the completion of 
the baseline studies (CFTR RNA and protein assays on brushed cells and IL-6 and IL-8 
levels in B AL fluid) and for the administration of vehicle to the superior segment of the 
RLL. The following four days will serve as the vehicle control period. If the patient's viral 
cultures from the nose, blood, urine, and stool are negative for infectious adenovirus and 
infectious AAV the patient will then proceed into the vector administration phase of the 
study. Intranasal doses of vector or vehicle will be given to the surfaces of the right and left 
inferior turbinates by catheter. The investigator will be blinded as to the assignment of 
vehicle and vector to individual nostrils to provide for non-biased nasal potential difference 
measurements. Endobronchial doses will be administered to the superior segment of the 
RLL. The nasal instillation will likely provide the best opportunity to detect vector activity 
due to the ease of access for cell samples and the reproducibility of TEPD measurements. 
The endobronchial instillation will provide the most relevant toxicity data. 
Studies will be performed at 3 days and 10 days post vector instillation. If viral cultures 
taken at day 10 are negative, the patient will be discharged without any further interventions 
or precautions. If cultures are positive from nose, urine or stool for recombinant AAV- 
CFTR vector at this time point, the patients will be instructed as to proper home precautions 
and decontamination procedures. AAV is generally transmitted via particles rather than 
aerosols and is easily decontaminated with ethanol or bleach. The likelihood of this 
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