Flowsheet of Studies after Adenoviral Instillation 
wtf ll 
Day 1 2 3 5 7 
9 11 13 
Nasal PD 
(same /contralateral) 
Nasal swab/wash* 
(same /contralateral) 
Pharyngeal swab 
(for virus) 
Bloodt 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
+ + 
Urine/stool + + + + + + + + 
(for virus) 
Nasal scrape + + + 
(same /contralateral) 
Nasal Biopsy + 
(same /contralateral 
* Inflammatory cells (neutrophils); cytokines (IL8-IL1); virus 
$WBC and differential daily; anti-Ad5CFTR antibodies day 7 and 15; 
Buffy coat for viral culture; Prothrombin time before biopsies. 
After viral cultures are negative on two occasions and discharge from GCRC 
is anticipated, patients will have repeat chest X-ray, spirometry, arterial blood gas. 
After discharge from the GCRC, patients will be followed on a weekly basis 
to monitor nasal PD (to test for duration of correction of bioelectric abnormalities) 
and to monitor nasal washes for evidence of inflammation until baseline status is re- 
estabished. 
Interpretation of data: 
These studies will provide information crucial to the safety of this 
recombinant virus, i.e., the possibility of local inflammatory response or systemic 
effects, and to whether this adenoviral vector can effectively correct the CF gene 
defect in the nasal epithelium, as indexed by changes in nasal potential difference 
and expression of CFTR mRNA and protein. It will provide information about the 
duration of any effect for correcting the gene defect. The study design employing 
escalating doses should provide information regarding dose-effect relationships for 
both efficacy and safety. 
The importance of these initial studies in gene transfer is that they are 
critical to define the safety of these vectors and to provide compelling evidence that 
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Recombinant DNA Research, Volume 17 
