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Researchers Externally Regulate Gene Implanted In Brain

By LESLIE H. LANG
UNC-CH School of Medicine

CHAPEL HILL, N.C. -- University of North Carolina researchers have used an antibiotic like an on-off switch to externally regulate a gene carried by a defective virus and implanted in the brain.

The accomplishment, made with laboratory rats, suggests that gene-transfer technology using the recombinant defective virus known as AAV (adeno-associated virus) may eventually prove feasible for gene therapy in human brain disorders such as Parkinson's disease and epilepsy.

A report of the new study appears Dec. 2 in the journal Gene Therapy.

The successful use of the tetracycline derivative doxycycline as a way to regulate a gene delivered to the brain via AAV also offers researchers a new tool for unraveling the complex molecular biology of neurological disorders and other conditions, including obesity, according to Dr. Richard J. Samulski, associate professor of pharmacology at the UNC-CH School of Medicine and director of the university's Gene Therapy Center.

"We're providing an offshoot from our clinically oriented efforts so that basic science researchers can now deliver a gene to an adult animal, turn a gene on and off and study its biology," Samulski says. He points out that the AAV gene transfer system used in the study may offer an alternative to the genetically engineered mouse strains that are developed to mimic human disease and gene defects.

"With this approach, you can establish if molecular principles that work in rodents would work in a larger animal, like dogs or monkeys. And that allows you to move into really relevant models quickly without having to be dependent on the genetic manipulation of embryos," Samulski says.

Rebecca P. Haberman, a UNC-CH graduate student in neurobiology, is the study's lead author. She is training in the laboratories of Samulski and Dr. Thomas J. McCown, research associate professor of psychiatry.

For the study, the UNC-CH tea
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Contact: Lynn Wooten
lwooten.est1@mail.unch.unc.edu
919-966-6046
University of North Carolina at Chapel Hill
1-Dec-1998


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