PATIENT BROCHURE 
INFORMATION FOR PATIENTS AND FAMILIES 
CONCERNING THE AAV-CYSTIC FIBROSIS GENE 
TRANSFER STUDY AT JOHNS HOPKINS 
THE BACKGROUND OF CYSTIC FIBROSIS AND THE PURPOSE OF THE STUDY 
Cystic fibrosis (CF), is caused by defects in a gene called CFTR. Abnormalities of this 
gene are fairly common in Caucasian Americans and North Europeans. If someone is bom 
with two abnormal copies of the CFTR gene (one from the mother and one from the 
father), that person will inherit the disease CF. The CFTR gene produces a protein that 
functions in the pumping of water and salt across mucous membranes in the nose, the 
bronchial tubes of the lungs, the sweat glands, the pancreas, and the reproductive tract. 
Persons with CF will often have problems in each of these areas. The sinuses are often 
blocked and infected. The lungs become plugged up with thick mucus and get infected. 
The sweat is more salty. The pancreas often does not work correctly, so that supplemental 
enzyme capsules may be needed for complete digestion of the food. Men with CF are 
usually sterile, and women may have mildly decreased fertility. There are simple ways to 
address many of these problems, including replacing pancreatic enzymes and taking in 
more salt and water to replace losses in the sweat. The lung disease due to CF remains a 
very significant problem for CF patients, despite advances such as antibiotics and better 
medicines to clear the lungs of abnormal mucus. 
Ever since the CFTR gene was discovered, scientists have been working to find ways to 
insert a normal version of the CFTR gene into lung cells, in the hope that the normal gene 
would correct the basic defect and allow for the production of normal lung mucus, which 
would no longer create obstruction and lead to infection. Scientists have used a number of 
gene carriers, called "vectors", to try to get the gene into the cells. Several of these vectors 
are derived from viruses which normally infect the cells of the nose and lung. These 
viruses have "learned" special means of inserting genes into cells. Several studies have 
focused on the development of adenovirus, a type of "cold" virus, as a delivery vehicle for 
the CFTR gene. These studies have had some success, but are limited by two factors. 
First, they are only temporary in that the genes are not permanently inserted into the 
chromosomes of the cell. Second, they have caused some inflammation in the lungs of 
animals and patients with CF when given at high doses. 
Over the last 5 or 6 years, the Cystic Fibrosis Research Center at Johns Hopkins 
University and the National Institutes of Health have collaborated with researchers at 
Targeted Genetics Corporation to develop an alternative vector based on a virus called 
AAV, which is naturally found in the nose and lung, but which does not cause disease. 
Unlike adenoviruses, AAV tends to be more long-lasting in its effects. Our group has 
tested altered versions of AAV which have had the virus genes removed and a normal 
version of the CFTR gene added. The altered virus has been able to insert the CFTR gene 
into cells in culture and into the lungs of animals (see Diagram 1). In the test tube, cells 
taken from the nose or lungs of CF patients have been corrected in terms of their ability to 
pump salt and water. In animals, the gene insertion has been long-lasting (up to 6 
months), and has not caused significant side effects. 
Recombinant DNA Research, Volume 20 
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