Scientific Abstra 
1. Scientific Abstract. Cystic Fibrosis (CF) is a common, lethal hereditary 
disorder dominated by respiratory disease. The purpose of this protocol is to 
evaluate the ability of repeat administration of a replication deficient re- 
combinant adenovirus (Ad) vector to safely and effectively transfer the normal 
human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the 
epithelium of large bronchi. The vector to be used, Ad^CFTR-lO, is an El* E3* 
Ad 5 -based vector with an expression cassette in the El region that includes 
the cytomegalovirus early promoter/enhancer, the CFTR cDNA, and the SV40 
stop/poly A signal. The study includes a total of 26 individuals treated over 
a period of 180 days. It will initially define the safety and pharmacodynamics 
of expression of the normal CFTR cDNA in the airway epithelium following sin- 
gle dose administration of ascending doses of the vector to the airways in 
different individuals. Once the dose schedules are defined, it will evaluate 
repeat administration at these doses, using extensive laboratory and clinical 
parameters to determine safety and surrogate biologic parameters to evaluate 
chronicity of expression. Relative to the Pi's ongoing study (Rockefeller Uni- 
versity IRB and Biosafety Committee RCR-029-0394 , NIH DNA Recombinant Advisory 
Committee (RAC) 9212-034, Food and Drug Administration (FDA) BB IND 4855) of 
in vivo Ad mediated CFTR cDNA transfer to the airway epithelium in CF, the new 
key elements of this study are: (1) administration of the vector to more lo- 
calized areas of the airways; (2) more careful definition of the pharmacody- 
namics of expression of the normal CFTR cDNA; (3) evaluation of expression of 
the normal CFTR cDNA following repeat administration; and (4) the use of a 
more active promoter/enhancer in the expression cassette. 
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Recombinant DNA Research, Volume 20 
