GMOs: The next generation

It sounded a little like Paris in St. Paul on a beautiful day this fall as officers for Cellectis, a French biotech company, announced the opening of its new plant sciences division at University Enterprise Laboratories (UEL).

Cellectis chose UEL as headquarters for its new division primarily because of the opportunity to work with Dan Voytas, professor of genetics, cell biology and development and director of the U of M Center for Genome Engineering. UEL’s relationship with the University and its location in the heart of agricultural biotechnology country were also attractions.

CBS Dean Bob Elde established UEL in 2002 with the help of corporate sponsors to provide a place where faculty could develop new biotechnology with commercial potential.

“I couldn’t be more pleased,” Elde said. “The partnership between Cellectis and Professor Voytas is a perfect example of the value UEL can provide to faculty, the University and the biotechnology industry.”

Voytas, who earned a B.S. at Harvard University and his Ph.D. at Harvard Medical School, did postdoctoral research at Johns Hopkins University and served on the Iowa State University faculty before coming to the University of Minnesota in 2008. His expertise using zinc finger nucleases to make very specific, targeted changes in genomes is well known in the scientific community. Voytas published research in Nature [April 2009] showing that zinc finger nucleases could make crop plants herbicide resistant with minimal changes to the plants’ own DNA and no use of foreign DNA.

Co-founded by scientists André Choulika and David Sourdive in 1999, Cellectis pioneered the use of enzymes called mega-nucleases in genomic engineering. The company, whose 120 employees include 45 with Ph.D.s, has since developed applications for medicine, research, agriculture and industry.

Nucleases work like scissors to cut and paste small, specific regions of an organism’s DNA to produce desired traits. This is a vast improvement over genetic engineering technology used since the1980s, which inserts foreign genes randomly and is more likely to produce unintended consequences. Zinc finger nucleases are hybrid molecules made by joining proteins found in cells to nucleases. Meganucleases are naturally occurring proteins.

“The simple explanation of the difference between the two technologies is that they provide different means to achieve the same end – a targeted chromosome modification,” Voytas says.

Cellectis has 53 “families” of patents for specific applications. They recently signed a license agreement with the University of Minnesota to produce and market TALENs (transcription activator-like effectors nucleases), a new genome engineering technology created by Voytas and a colleague at Iowa State University to modify specific genes in a cell.

At the open house, Voytas spoke about the increasing pressure on plant sciences to meet needs of the growing global population as land for growing food and energy crops shrinks. Using a slide of the University’s new stadium to illustrate his point, he explained that agricultural land per capita worldwide is now about the size of the stadium, but by 2050 will only be one-third that size. He believes genomic engineering could make crop plants more productive and better for the environment because they will require less chemical fertilizers and pesticides and have less of an impact on soil.

“I’m optimistic that we can do it,” he said. “Just look at how we’ve increased plant productivity over the past 100 years with hybrids, the green revolution, and transgenics,” he said. “Ninety percent of soybeans and 80 percent of corn in Minnesota are now genetically modified.” The new genome modification technologies, he says, are more respectful of nature than traditional genetic engineering because they are more targeted.

“An organism’s genome changes continuously to adapt to differences in climate and other conditions,” he says. “In contrast, genome engineering is a directed, deliberate way to introduce genetic variability,” Voytas said. “That’s not to say there aren’t risks, but risks need to be assessed on a case by case basis whether a plant is altered by traditional breeding or genomic engineering. It’s important to make sure the new trait won’t have harmful consequences.”

In the short-term, the Cellectis’ Plant Sciences Division plans to create genetic traits, most likely for corn and soybeans, for established agricultural biotech companies. Voytas’ longterm plan is to use Arabidopsis thaliana (a model for crop plants) and tobacco, also a useful model, to develop desirable traits for rice and tomatoes.  

Voytas grew up in northern Minnesota, where his father was a forester with the US Forest Service. The family lived in towns near the Superior and Chippewa National Forests. He became interested in plant biology and agriculture through his father.

“I was an undergraduate in the early 1980s, when biotechnology was really just starting to take off,” he says.  “I was excited by the possibilities and the marriage of biotech and plant science worked for me.”

– Peggy Rinard