U Of M-developed gene editing technologies making waves in Agriculture, Medicine

Date:10-13-2016

Gene-editing technologies, such as those coming out of the University of Minnesota, have only so far hinted at their potential to disrupt the agricultural and biotechnology markets in a major way with their ever-expanding applications in plant genetics and human disease research.

But realizing that potential may not be as far off as once thought: Companies in the gene-editing space rush are even now rushing to raise investor cash as they figure out new ways to apply the technology to new sets of challenges. One such is the French company Cellectis SA (Nasdaq: CLLS), which holds the license to a type of gene-splicing tool developed by Dan Voytas, director of the U of M’s Center for Genomic Engineering.

Cellectis pulled off a $228 million initial public offering last year, which it is using to fund the application of Voytas’ tech, called TALENs, to human cancer immunology. The company says TALENs can be used to genetically alter donated CAR T-cells—a key component of the body’s immune system—to make them seek out and destroy tumor cells in patients.

TALENs is an acronym for the DNA-cutting enzyme “transcription activator-like effector nucleases.” Its potential in the human health field was highlighted last year when the leukemia of a one-year-old girl was put into remission after receiving donated T-cells that were modified using technology.

The Cellectis trial was just the second-ever for gene editing as a human health therapy—its backers say TALENs and an even newer technology called CRISPR (“clustered regularly interspaced short palindromic repeats”) could open the door to applying gene editing to HIV, hemophilia, muscular dystrophy and other ills not yet even imagined.

Invented in 2009 by Voytas and Adam Bogdanove of the University of Iowa, TALENs’ original application was in plant sciences, and that is where the immediate benefits for Minnesota are coming from.

Voytas, in addition to his role at the U of M, is the chief scientific officer of Calyxt, a subsidiary of Cellectis, which focuses on using the tool to improve food crops. It is part of emerging coterie of gene editing companies linked to the U of M’s Center for Genomic Engineering that are marking the state as a player in the field.

Some of the others include Recombinetics Inc., B-MoGen Biotechnologies Inc., and ApoGen Biotechnologies.

Voytas told TCB that when it comes to applying gene-editing technology to agriculture, the state is well positioned.

“The leading companies in animal agriculture (Recombinetics) and plant genetics (Calyxt) are located here,” he said. “Both companies are ahead of the curve. The Monsantos, the DuPonts, the Syngentas and other big players are all beginning to be interested in jumping into this space, but we already have hundreds of acres of soybeans being grown.

“It’s already happened in the ag applications, and we’re leading the way.”

Cellectis has shown its faith in Calyxt by moving to create a new corporate headquarters for its subsidiary in Roseville, including up to five acres of agricultural test fields, greenhouses and a 40,000-square-foot combination research lab/office building. The test plots and greenhouse are already in use, Voytas said, when the lab building to come later in a second phase.

He said the advantage TALENs and other gene-editing tools bring to engineering such foods as reduced trans-fat soybeans and potatoes that can be cold-stored longer is that they aren’t considered “genetically modified” by the U.S. Food and Drug Administration. That’s because unlike controversial GMO foods, there is no introduction of foreign DNA into the plant genome, such as is done to enhance the ability to crops to resist pesticides.

Instead, the gene-editing process is used only to strategically deactivate genes to achieve desired traits, such as to produce less fat in a soybean, thus is seen as essentially no different from naturally occurring mutations.

In both agriculture and medicine, the potential of gene-editing tools like TALENs and CRISPR are just now being imagined, and with further investment are likely to profoundly change the course of science, Voytens predicted.

“It’s really transforming life science research,” he said. “To me, an apt analogy is when the silicon chip was invented. No one then ever envisioned we’d be carrying sophisticated devices like iPhones or laptop computers that could connect us to the world as a result of that invention.

“I think now, TALENs and CRISPR are like the chips were. Yes, they’re allowing us to do remarkable things at present, but it’s hard to imagine just how they’re going to benefit us in the future. We do know they’re definitely going to change technology and provide new opportunities for human therapeutics.”