Cystic fibrosis is an autosomal recessive genetic disease caused by defective salt and water 
transfer across the cells of the lung and other organs. The disease affects the lungs, digestive 
system, and sweat glands, as well as other exocrine glands, such as the lacrimal glands and 
salivary glands. The greatest pathology occurs in the lungs where dysfunction of small airways 
and recurrent infections cause progressive obstructive pulmonary disease, hypoxemia, and 
eventually carbon dioxide retention, right ventricular failure, and death. The isolation of the 
gene for cystic fibrosis (the CFTR gene) has led to the possibility of correcting chloride 
secretion in the lungs of these patients with normalization of airways function. In this protocol, 
we propose to evaluate the safety and efficacy of gene therapy in cystic fibrosis using a 
recombinant adenovirus that is made replication deficient by deletion of the El region. It will 
be used to deliver the CFTR cDNA to the nose, trachea, and one lobe of adult cystic fibrosis 
patients with mild to moderate disease. We propose to study the safety and efficacy of three 
different doses of this construct in groups of five patients. The patients will be treated with the 
ad-CFTR construct and followed for evidence of gene expression, evidence of correction of 
physiological function of cells, and evidence of improvement in salt transport and mucous 
clearance in the treated regions of the lung. Patients will be studied for adverse reactions to the 
virus, duration of the expression of the gene, duration of correction of function, and 
immunological responses to the construct. After eight weeks, they will be treated again to 
establish whether the construct will work on a repeated basis and whether there is any toxicity 
associated with repeated administration. 
[354] 
Recombinant DNA Research, Volume 17 
