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Gene Therapy Incorporates Molecular Rheostat For Controlled, Long-Term Drug Delivery

Using a unique combination of innovative technologies, scientists have demonstrated the ability to introduce therapeutic genes into the body and then, further, to precisely control the activity of those genes with a drug that could be given as a simple pill.

The novel gene therapy system, developed by researchers at the University of Pennsylvania Medical Center and ARIAD Pharmaceuticals in Cambridge, MA, represents an entirely new form of drug delivery, one that opens the door to many therapies not previously possible. A report on the experimental study, performed in mice and monkeys, will appear in the January 1, 1999, issue of Science. (Copies of the final version of the paper are available to reporters through the journal's news office at 202-326-6421.)

"We're excited about these results, because they create many new opportunities for experimental and then clinical applications of gene therapy that we couldn't consider before," says James M. Wilson, MD, PhD, director of the Institute for Human Gene Therapy at Penn and senior author on the report. "This system will allow us to modulate the expression of a delivered gene in response to changes in a patient's disease."

The new system couples advances at Penn allowing the long-term introduction of genes into the body with a patented technology (ARGENT) to regulate gene activity from ARIAD.

As the culmination of several years of concerted effort, Penn researchers recently succeeded in optimizing a gene therapy viral vector to achieve long-term protein production without sparking an immune-system reaction. The vector is an engineered version of a virus known as adeno-associated virus, or AAV, which is a very small, innocuous virus.

For this project, the Penn and ARIAD scientists stripped two AAVs of their viral genes and reloaded them respectively with the gene for erythropoietin, or Epo, a recombinant protein that stimulates red blood cell product
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Contact: Franklin Hoke
hokef@mail.med.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
1-Jan-1999


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