Non-Technical Abstract 
Adenovirus-Mediated Gene Transfer for Cystic Fibrosis: Safety of Single Aerosolized Administration to the Lung 
DESCRIPTION OF THE PROPOSED EXPERIMENT IN NON-TECHNICAL LANGUAGE 
Cystic fibrosis (CF) is a common inherited disease among the white population of Europe and North America, ft is 
characterized by chronic infection and obstruction of the airways leading to the lungs. Patients commonly die from the 
disease by their mid-to-late twenties. The recent discovery and characterization of the inherited material — the r^ne — 
that causes the disease has led to a rapid increase in our knowledge of the basic defect responsible for the disease 
state, and has raised the possibility of treating CF by giving to the patient a good copy of the CF-associated gene. This 
is a new approach to the treatment of inherited diseases, called gene transfer. 
Eventually gene transfer for cystic fibrosis might be achieved by treating the airways of CF patients with a “tailor-made" 
virus that has been altered to make it less infectious and to include the CF gene. One possible virus to do this is called 
adenovirus. It is normally associated with minor respiratory infections, such as colds. Although adenoviruses have 
been used safely in the past as vaccines, we need to establish the feasibility and safety of using such an approach for 
treatment of cystic fibrosis. 
The sponsors of this proposal have already treated eight CF patients with very small amounts of CF-adenovirus and 
shown it is possible to correct the basic defect associated with the disease. In two studies virus was applied to a small 
area within the nose and a small electrode used to measure the tiny voltage that normally exists across the lining of the 
nose. In patients with CF, this voltage is abnormal because of a defect in the CF gene. After administration of virus, 
this voltage was temporarily restored to normal. 
We are extending these studies to ascertain whether it is safe to administer virus to the lung in amounts that are 
believed to be large enough to correct the defect in the CF gene, and whether virus can be introduced safely into the 
lung by aerosol treatment — breathing in a mist of virus . The first study, "Adenovirus-Mediated Gene Transfer for 
Cystic Fibrosis: Safety of Single Administration to the Lung" will evaluate administration of the virus to a small part of 
the lung (a lobe) by a bronchoscope, a tube commonly used in pulmonary medicine which allows visualization of the 
airways. If no problems occur after a total of six patients have received two different doses (3 in each dose group), this 
aerosol study will begin. By testing aerosol administration of the virus the lung, starting with small doses, we can leam if 
this widely used and noninvasive method of lung treatment can be safely used with our virus vector. In this way, we 
hope to maximize patient safety, while at the same time determining whether adenovirus is likely to be safe for use in 
CF patients. 
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Recombinant DNA Research, Volume 20 
