these studies to understand safety, efficacy, and potential dosing intervals pertinent 
to this novel mode of therapy. 
Non-technical 
Cystic fibrosis (CF) is a genetic disease that affects ~ 1 in 2,500 live births in 
the United States. The gene that is abnormal in CF produces problems particularly 
in the tissues that line various body cavities. Generally, these tissues, termed 
epithelia, secrete a combination of water and mucus to protect the surfaces of these 
tissues from toxic/ environmental insults from the outside world. These fluids are 
abnormally secreted and cleared from the lungs of CF patients, which leads to a 
chronic cycle of bacterial infection and damage of airway walls. Ultimately, most 
deaths from CF ( > 95%) result from lung tissue destruction and pulmonary failure. 
The current therapies for treating CF lung disease focus on promoting 
clearance of secretions from the lungs and antibiotics designed to control the lung 
infection. Whereas these therapies have been effective in prolonging the life-span 
of CF patients to a median age of ~25 years, they have reached their maximum 
benefit. A recent series of studies in the laboratory has shown that if the normal 
version of the CF gene is inserted into CF cells, a correction of the epithelial defect 
in these cells is readily detected. This type of experiment, in which a gene (the 
normal CF gene) is transferred to a defective (CF) cell, is a type of gene transfer 
and has raised the question of whether similar types of gene transfer may be utilized 
clinically for therapy of CF lung disease. 
The adenovirus is a "cold" virus that has a natural tendency to infect many 
tissues of the nasal cavity and lung. This feature, plus the ready access of the lung 
tissues to delivery of this kind of virus via aerosol or direct liquid instillation, 
indicates that this virus is potentially useful for delivering the normal CF gene 
therapeutically to the CF lung. Consequently, this virus has been genetically 
engineered by recombinant DNA technology so that some of the potentially toxic 
components of this virus have been removed and the normal copy of the CF gene 
inserted. A series of studies in animals and in human tissues in laboratory culture 
have shown that this virus appears to be very effective in introducing the normal CF 
gene into affected tissues without any major detectable toxic effects. In the current 
study, we plan to test this virus vector in the nasal cavity of CF subjects. The major 
focus of the study is designed to test whether the administration of this virus to a 
very localized region of the nasal cavity is safe, and whether it has the capacity to 
restore the functions of the nasal lining tissue to normalcy. The nasal cavity was 
chosen for these initial studies because of the small volume of virus needed to 
perform the tests, the fact that the nasal lining tissue exhibits the same types of 
abnormalities as are expressed in the lung, and that testing the effects of the virus 
can be performed repetitively with relatively little discomfort to the patient. The 
long-range goal of these studies is to test the feasibility of this type of virus for gene 
therapy of CF lung disease and to develop information that will lead to the design of 
better viruses and better modes of delivery. 
Recombinant DNA Research, Volume 17 
[433] 
