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U researchers use new technique to manipulate genes

The method has opened more possibilities for plant biologists.
April 29, 2009

A study published Wednesday in the international weekly journal Nature details a University of Minnesota researcher’s method of manipulating plant genes with a custom-made enzyme that could make plant products more useful.
Dan Voytas , a co-author of the paper and director of the Center for Genome Engineering at the University, and his colleagues used zinc finger nuclease, or ZFNs, to make tobacco plants resistant to herbicide. Voytas said the technique benefits plant biologists by giving them an opportunity to understand processes in plants and apply their findings to make plant products more functional for food or industrial use.
Voytas knew a colleague in Utah had used ZFNs on fruit flies; he was able to adapt the technique for use in plants.
In the paper, researchers explained the difficulty plant biologists encountered when trying to efficiently modify plant genes. As opposed to previous methods, ZFNs are more precise because they can be customized for a particular gene sequence, the study concluded.
Currently, most herbicide-resistant plants are modified using a foreign gene, Voytas said. Instead, he and his fellow researchers “modified a naturally occurring plant gene to make the plant herbicide resistant.”
Though ZFNs were introduced in 2002, they were not readily available to academic researchers, Voytas said.
In response, a group of scientists formed the Zinc Finger Consortium , including Voytas, to make a ZFN that would work for their purposes.
The group understood basic necessities for making the reagents, but needed to find a more reliable process. Upon its success, the consortium made the method openly available to researchers at no cost.
Nathan Springer , assistant professor in plant biology, is currently studying the effects of genetic mutations in corn. Though he did not participate in Voytas’ research, he expressed interest in the prospective applications of a more widespread access to ZFNs. He said technology preceding ZFNs lacked accuracy and did not allow scientists to target a specific gene.
“Right now, a lot of things people do in plant genetics are random as far as whether they happen or not or where they happen. Zinc fingers give the ability to target things to a specific place on a chromosome,” Springer said.
“This opens up a new era among plant scientists; a new way to monitor plant genes and genomes,” Voytas added.

A safer and smarter way

The potential of ZFNs reaches far past the mutation of plant genes. Voytas also cited the possibilities in human genes.
Jakub Tolar , assistant professor of pediatrics, uses ZFNs to treat inherent diseases in adolescent patients. Though this has not reached clinical trials yet, Tolar said it has greater viability than other gene therapy techniques.
Alternative methods correct defects by inserting or replacing the gene, Tolar said.
Voytas said these methods are less reliable because it is uncertain where the newly inserted DNA will land on the chromosome. It is also uncertain whether or not the new gene will function properly. It could even cause further mutations, he said.
ZFNs go to the exact place and change the defective gene, Tolar said.
Tolar emphasized the importance of making ZFNs available at the clinical level. He commended the work of the consortium in addressing this issue. While private companies may be more interested in what will make the most money, the consortium realizes the importance of what has clinical potential, he said.
“This is the safer gene therapy,” Tolar said. “This is the safe way and smart way of doing gene therapy.”

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