M J. Welsh and A.E. Smith - RAC Application 
APPENDIX 6 
Description of the Proposed Experiment in Nontechnical Language 
Cystic fibrosis (CF) is the most common inherited disease among the white population of 
Europe and North America. It is characterized by chronic infection and obstruction of the 
airways leading to the lungs. Patients usually die from the disease by their mid twenties. The 
recent discovery and characterization of the inherited material - the gene - that causes the disease 
has lead 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 
therapy. 
Eventually gene therapy 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 test the feasibility and safety of using such an approach. 
This proposal is to treat three CF patients with very small amounts CF-adenovirus and to 
test whether we can measure correction of the basic defect associated with the disease. Virus 
will be applied to a small area within the nose and a small electrode will be 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. 
We hope to be able to measure such voltages in CF patients treated with the virus just as 
we have been able to do using cells taken from the nose of patients and grown in the laboratory. 
This will be the first step in developing CF gene therapy. We will also do extensive tests to 
establish whether the treatment was safe. If this is the case, we shall plan to extend the study to 
treat larger areas of the lung. 
Recombinant DNA Research, Volume 16 
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