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Genetic on-off switch found at Purdue could turn on gene therapy

WEST LAFAYETTE, Ind.--A Purdue University researcher studying genetic on-off switches in yeast found a system that could be useful in human gene therapy.

Gunter Kohlhaw, a recently retired Purdue biochemistry professor, envisions a time when gene therapy will alleviate suffering from diabetes mellitus, familial gout, hypercholesterolemia or any of the other 400-plus diseases caused by an underlying genetic deficiency. But in many cases, before gene therapy can work efficiently, doctors must find genetic switches to turn therapeutic genes on and off. Such switches let them regulate levels of compounds like insulin in diabetics.

Kohlhaw and his co-workers have found one switch that looks promising.

"We have a system that is in its infancy, but which conceivably could be useful in mammals," Kohlhaw says. "We know it works perfectly in cultured mouse cells."

Other on-off gene switches already exist, but they depend on hormones or the antibiotic tetracycline. People have to eat or get an injection of a hormone or antibiotic to turn the therapeutic genes on or off, and some people can't or don't want to risk side effects associated with those compounds.

Because the compounds that make up Kohlhaw's gene switch are natural components of yeast, they shouldn't affect human health, he says, although researchers need to test them to be sure. Both compounds are part of the yeast's system for producing leucine, an amino acid essential to human health.

"What's really unique about the system is that it's not present in humans, so it can be genetically engineered in human cells and completely controlled from the outside," says Michael Hampsey, a professor in the Department of Biochemistry at the University of Medicine and Dentistry of New Jersey. "It could be used in gene therapy and other systems where tight control over gene expression is critical."

The on-off switch discovered by Kohlhaw and his co-workers at Purdue consists of two m
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Contact: Rebecca J. Goetz
rjg@aes.purdue.edu
765-494-0461
Purdue University
12-Oct-1999


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