Yale Bulletin and Calendar

November 15, 2002|Volume 31, Number 11

Researchers create artificial
'light switch' to regulate genes

A Yale researcher and his collaborators have succeeded in creating an artificial transcription factor -- a kind of light switch that turns genes on and off -- and induced the growth of new blood vessels in a live laboratory mouse, it was reported in the journal Nature Medicine.

"This is the first time that we have been able to design and use an artificial transcription factor to regulate a gene in any animal," said the senior author of the study, Dr. Frank Giordano, assistant professor of medicine, director of the Yale Vector Core of the Yale Cancer Center and director of the Cardiovascular Gene Therapy Program. The journal article was made available online this month and is scheduled for publication in December.

Giordano says the same approach could work in humans, but that first researchers must do more research and toxicology studies to insure patient safety.

"This approach represents a new paradigm in gene therapy that is predicated on the modulated expression of endogenous genes," the researchers wrote in the study.

The zinc finger protein (ZFP) transcription factor used in the study was designed by Sangamo BioSciences of Richmond, California, and several of the company's scientists are co-authors of the study. The ZFP is one of four common structural themes for protein structures that bind to DNA and generate cell production.

In the study reported in Nature Medicine, Giordano constructed and used viral vectors to introduce the artificial transcription factors into laboratory mice and induced the growth of new blood vessels in the animals' ears. The procedure also promoted healing of wounds.

The researchers said that, based on the results, there appeared to be several advantages to using an artificial transcription factor over conventional gene therapy, where patients are injected with DNA encoding a single gene product in hopes of stimulating growth. The new blood vessels in the study appeared to be more mature than those induced by standard gene therapy.

"Complex processes such as blood vessel growth and wound healing involve multiple genes and splice variants," Giordano says. "Using the ZFP approach, multiple separate genes can be regulated with a single therapeutic intervention."

He adds, "These studies establish, for the first time, the feasability and potential utility of this approach in vivo."

-- By Jacqueline Weaver

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