Precis 
This protocol is an initial safety and biologic efficacy study to evaluate the 
use of the replication deficient recombinant adenovirus AdCFTR to transfer the 
normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA 
to the respiratory epithelium of adults with cystic fibrosis (CF) . If 
successful, this strategy has the potential to form the basis of therapy to 
prevent the respiratory manifestations of CF, thus alleviating the major cause 
of morbidity and mortality of this common hereditary disorder. The overall 
design is that of a combined ascending dose toxicity study and biologic 
efficacy study with the patients serving as their own controls. Following a 
baseline evaluation period and a vehicle control period, AdCFTR will be 
administered to the left nostril and, one day later, to the left large 
bronchi. Five groups will be studied (n=2 each group), with each group 
receiving increasing amounts of AdCFTR. At the completion of the study, the 
following questions will be answered: (1) Is it safe to administer a vector of 
the design of AdCFTR to the respiratory epithelium in CF? ; (2) Will AdCFTR 
correct the biologic abnormalities of CF in the respiratory epithelium?; (3) 
How long does the biologic correction last?; (4) Is the correction sufficient 
to correct the abnormal electrical potential difference of the airway 
epithelial sheet?; (5) Is there improvement in clinical parameters relevant to 
the disease process?; and (6) Does humoral immunity develop against AdCFTR 
sufficient to prevent repeated administrations in the future? 
Recombinant DNA Research, Volume 16 
[617] 
