CRISPRing future harvests at DuPont

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CRISPR is set to make its commercial debut in maize fields in 2020. The honor (and burden) of probing the market, as the first product developed with the revolutionary technique for genome editing, is up to a kind of corn called waxy for the appearance of its kernels. Its starch is almost entirely amylopectin and almost zero amylose. Conventional waxy varieties already available to farmers have some yield drag due to the undesirable genetic baggage introduced by breeding. Conversely, DuPont Pioneer researchers created a waxy version of their best corn without yield drag or foreign DNA by editing out a gene for an enzyme that produces amylose. Amylopectin is used for the production of goods such as paper adhesives and food thickeners. What remains after its extraction is a protein flour that can be employed as feed. It may sound like a low-profile debut for the celebrated genome editing technology that is asked to succeed where GMOs have failed: gaining consumer confidence. But this is a deliberate strategy, as explained below by Neal Gutterson, DuPont Pioneer’s vice president of R&D.

Neal Gutterson picYour waxy corn will be mentioned in books on the history of biotechnology for its pathfinder role. Why did you choose it as a kickoff?

CRISPR-Cas technology is certainly a breakthrough in biology and one that will make significant improvements to agricultural product development over time. At DuPont Pioneer, we are committed to fully realizing its potential and, in our opinion, it requires a measured approach to the first products to be commercialized. We purposely chose to apply CRISPR-Cas to improve waxy corn hybrids, a familiar product already on the market. Starting with an identity-preserved product as our initial CRISPR-Cas offering allows us to lay a solid foundation for success for future, larger-volume products of this plant breeding innovation.

DuPont Pioneer is an early mover in the CRISPR world and has entered a strategic alliance with the trailblazer company Caribou Biosciences. How soon did you sense the revolution coming?

My role was leading a small ag biotech company mostly focused on biologicals. By early 2013 I was increasingly becoming aware through articles in the scientific press and literature that CRISPR-Cas9 was going to replace all earlier tools for genome editing. I recognized that this breakthrough would indeed change the way we improve crop genetics. This was great motivation for me to return to a career focused on agricultural biotechnology and genetics. When I was approached about a role at DuPont Pioneer in 2014, and I became aware the company was already deeply engaged with CRISPR-Cas, I became even more convinced to join and help lead the company to deploy the technology.

Should we expect small incremental steps or can we hope for a quantum leap forward? One of the problems of agricultural biotechnology is that benefits are more apparent to producers than to consumers.

At DuPont Pioneer, we are exploring applications in all crops that we work in – corn, soybeans, rice, wheat, canola, sunflowers. Targets such as disease resistance, drought tolerance, yield stability, improved output traits like healthier oils or higher protein are certainly among the top on our initial list. There are exciting opportunities that the produce industry could also deliver upon, including improved taste and longer shelf life. However, we like to view the opportunities presented by CRISPR-Cas in terms of time horizons, and these would best describe what the agriculture industry could expect to achieve in the near- to mid-term. Longer-term we can imagine revolutionary developments such a dry-seeded rice to enable rice growing regions to dramatically reduce water usage in this currently very water-intensive agricultural system.

The new CRISPR website launched by DuPont Pioneer stresses that  “products developed using CRISPR-Cas advanced plant breeding only include genetic material from the target plant/crop.” Are you using only rice genes for rice, maize genes for maize, etc. to differentiate CRISPR from GMOs?

Applying CRISPR-Cas as a tool for targeted plant breeding to deliver products that are similar to, or even indistinguishable from, varieties developed from traditional plant breeding methods represents a big step change for agriculture in terms of greater quality, accuracy and more efficient timelines. These applications are when we only work with the natural diversity available within the specific plant genome. It’s important to note that CRISPR-Cas can also be applied to improve the development process for GMOs which incorporate genetic sequences sourced from outside of the specific plant’s gene pool. This is necessary if the solution is not readily available within the plant. Examples include insect control and herbicide tolerance. In these cases, the products are still considered GMOs.

Questions of fairness have fuelled the GM controversy, i.e. few multinational corporations controlling the global food market. Is CRISPR changing the landscape of players in R&D worldwide?

CRISPR-Cas is not only the province of the few, big agricultural companies. Due to its relative simplicity, it is very much a democratic technology, and we see the full range of small and big companies, academics and public research institutes all applying CRISPR-Cas to solve their most difficult challenges. Our public/private partnership with CIMMYT is an excellent demonstration of how we can collaborate with CRISPR-Cas for the benefit of smallholder farmers in Africa. Our first project is aimed at addressing a particularly devastating disease in maize experienced in Sub-Saharan Africa called Maize Lethal Necrosis. As a member of the board at CIMMYT, their work is very near and dear to my heart.

Some time ago we interviewed Sanjaya Rajaram, one of the fathers of the Green Revolution, asking him to make three wishes. The same question for you: if a genie were to grant you three wishes, what would they be?  

One: that CRISPR-Cas would be a biological and social catalyst for a new green revolution contributing to a healthier food supply produced in a healthier manner, especially for smallholder farmers around the world. Two: a basket of (great tasting) heirloom produce that is much more affordable than ever before, and produced with less pesticides than ever before. Three: that my granddaughters will grow up in a world in which they as women will have equal opportunity with men to contribute to improving our future on this planet.  

(in the gallery: examing plantlets, controlled environment growth chamber, sequencing lab; credit DuPont Pioneer)

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