VII.C. Potential Benefits 
This is a phase I study so there will be no actual benefits to the patients 
involved in the experimental protocol. This study could have enormous benefit to 
the larger community of CF patients for a variety of reasons. Despite tremendous 
investment of resources by the pharmaceutical industry, management of the 
pulmonary complications of CF is inadequate; patients typically succumb to these 
complications by the age of thirty. The information gained in this study will provide 
information that is critical to the eventual development of effective treatments of 
the lung disease of CF by gene therapy. We hope to evaluate the overall safety of 
this approach as well as to assess the feasibility of obtaining genetic reconstitution 
that is therapeutic and stable. We do not believe that this trial will actually be 
therapeutic to the patient because the therapy will be administered to the nasal 
cavity. 
We consider this an extremely important study with respect to evaluating the 
potential use of recombinant adenoviruses in the treatment of cystic fibrosis. We 
would consider this a successful experiment if we can answer the critical questions 
addressing the safety and efficacy of this approach to gene therapy in cystic fibrosis. 
However, based on our extensive work in animal models we believe there is a 
reasonable chance that the study will show recombinant adenoviruses are capable of 
safely transferring recombinant CFTR genes to the cystic fibrosis nasal epithelium 
and that the genes function for a prolonged period of time. 
An important barrier to gene transfer into the surface epithelium of the 
airway is that the cells are relatively quiescent with approximately 0.1% of the cells 
going through the cell cycle at any one time. For this reason, approaches to gene 
therapy which depend on integration of the transgene into the recipient cell’s 
chromosome, such as recombinant retroviruses, likely will not be effective in adults. 
Recombinant adenoviruses have the capability of transducing genes into 
nondividing cells and maintaining the transgene as an extrachromosomal element. 
We have used the human xenograft system to evaluate the stability of adenoviral 
mediated recombinant gene expression. We have found that recombinant 
adenoviruses are capable of efficiently transferring genes into nondividing fully 
differentiated cells of the surface epithelium and that the recombinant gene 
expression is stable for the longevity of the grafts which is approximately 4 weeks. 
Presuming the viral genome is stable in the cell, the persistence of recombinant 
gene expression becomes dependent on the lifespan of the cell. As described above 
the cells of the surface epithelium have a relatively long life span and xenograft 
experiments have demonstrated gene transfer into all cell types that line the lumen 
of the airway. 
Recombinant DNA Research, Volume 17 
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