MJ. Welsh and A.E. Smith, RAC Application 
clinically evaluated at three to four week intervals until you are given the altered virus. 
The wait from the time of enrollment into the study and administration of the altered 
virus will be at least six weeks, but could be significantly longer. Most of the tests will 
be repeated just before you are given the altered virus, and some will be repeated during 
the visits between enrollment into the study and administration of the virus. 
The virus, known as adenovirus 2, is a common virus that is found in human airways and 
can cause a "cold". The virus that you will receive has been altered so that it cannot 
reproduce normally. These changes limit its ability to ca use d isease, to grow, and to 
spread. The normal gene for the cystic fibrosis protein, CFTR, has been inserted into the 
virus. In the laboratory, it has been shown that this altered virus can enter the cells that 
form the lining of the human nose and deposit the normal gene, so that normal CFTR is 
produced by the cells. Studies with laboratory animals suggest that the altered virus does 
not cause disease or illness. They also indicate that the virus can carry a new gene into 
the cells of the airway. 
The day the virus is applied, you will be admitted to the hospital. The virus you will 
receive has been prepared at Genzyme Corporation in Framingham, Massachusetts. To 
put the virus into the lining of a small part of the nose, we will initially numb the interior 
of your nose with a few drops of Lidocaine (a common numbing medicine) and give you 
a mild tranquilizer that will reduce anxiety and help you sit still for 60 minutes. By 
placing a small plastic ring in the inside of your nose, we will instill a small amount of 
liquid that contains the altered virus with the CFTR gene Each area will be about half 
the size of a dime. Afterwards the excess virus will be removed by suction and washing. 
This procedure will be performed in both nostrils. Different amounts of the virus will be 
used in different patients to determine how much of the virus is needed to adequately 
produce the CFTR protein and to determine safety of the application. This procedure is 
experimental. 
To determine whether the virus carrying CFTR can correct the cystic fibrosis 
abnormalities, and to determine its safety, we will perform several studies on days 1, 2, 3, 
5, 7, 9, 11, 13 and 15 and at one to two week intervals for eight weeks after discharge 
from the hospital. We will take swabs from both nostrils and your throat and brushmgs 
from the inside of your nose. The nasal and pharyngeal swabs are performed by gently 
rubbing a cotton-tipped applicator in the inside of your nose and in your throat. These 
procedures are commonly performed to diagnose "strep throat" and are not harmful or 
painful. The nasal brush will be performed after numbing the inside of the nose with a 
numbing medicine (Lidocaine). We will rub a small brush over the inside of your nose 
for about 10 seconds, so as to scrape off some cells from the lining of the nose that was 
exposed to the virus. We will study these cells in the laboratory. This procedure is 
experimental and may be slightly painful. The discomfort could last for several hours but 
should be minor. You will be able to request over-the-counter pain killers as needed. 
Because this is an experimental virus, there is a possibility that inflammation of the lining 
of the nose may occur. It is possible that redness and pain could occur or that you could 
develop symptoms similar to those experienced when you have a "cold." To determine if 
any harm was done to the area of nose where the virus was given, we will perform a nasal 
biopsy. Prior to the biopsy, an anesthetic to numb the feeling in the area will be used. A 
small area (about half the size of a dime) will be excised by an Ear, Nose and Throat 
doctor. 
To learn whether the experimental virus can correct cystic fibrosis abnormalities, we will 
measure the voltage across the lining of the nose. This involves the application of a self- 
adhesive patch to your skin, and touching the inner surface of the nose with a small 
Recombinant DNA Research, Volume 16 
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