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Genetic modification, modified

April 29, 2009


Dry tobacco leaf.

University and Massachusetts General Hospital researchers used a new method of genetic modification to alter a single gene in tobacco plants.

A new technique allows precision gene modification in plants

By Deane Morrison

The controversy surrounding genetic modification of plants stems partly from the way it's done: Genes are introduced in scattergun fashion, with little control over where they integrate into the genome and what effects that may have.

But a new, precise method promises to restore much of that lost control. Developed by University of Minnesota and Massachusetts General Hospital researchers, it uses an enzyme that reads DNA like Braille and makes pinpoint changes in the gene targeted for modification.

In a paper published April 29 online in Nature, a team led by University of Minnesota researcher Daniel Voytas describes how they used the method to engineer tobacco plants for resistance to herbicide. Only one gene was changed, and no genes were added to the plant's chromosomes.

The method has potential for changing the way researchers approach a host of tasks, such as making crops more nutritious or resistant to adverse conditions, coaxing algae to produce more biofuel, or even curing diseases in humans and other animals.

"My colleagues and I demonstrated the first use of the technology in plants, and we and others have shown it to work in human cell lines and other animal models, such as fruit flies and roundworms," says Voytas, a professor of genetics, cell biology and development and director of the University's new Center for Genome Engineering.

"The method offers enormous potential for gene therapy, and its advantage is its precision."

The enzymes at the heart of the technology are known as zinc finger nucleases, or ZFNs. In doing their job, ZFNs explore the DNA in a cell nucleus, probing with extensions—"zinc fingers"—until they find the particular DNA sequences they have been designed to ferret out. They then chop those sequences out of the chromosome, replacing them with new sequences—provided by the researchers—that confer herbicide resistance or other traits.

In the case of the tobacco plant, "the modified gene is a widely used target for herbicides," says Voytas. When functioning normally, the gene instructs the cell to make a protein that's crucial for life but that can be disabled if a herbicide molecule attaches to it.

But the modified gene instructs the cell to make a slightly altered version of the protein, one that can still perform its cellular duty but offers no foothold for a herbicide. And so the plant becomes herbicide-resistant.

Voytas is now testing the method in rice, the world's most important crop; a member of the mustard family called Arabidopsis, a widely studied model plant; and algae with the potential to produce biofuel. If successful, ZFNs could become the tool of choice for getting more bang for the agricultural buck.

Or, as Voytas puts it, "The technology is ready for prime time."