AgBio Companies Embrace Gene Editing for Stronger Food Future

Gene editing technologies have been used to improve agricultural products for more than two decades. One of the earliest editing technologies was Transfer DNA, T-DNA, which is extracted from Agrobacterium tumefaciens, a tumor-causing bacteria that infects plants and injects its DNA into their cells to reproduce.

Julien Curaba, PhD, chief scientific officer at Eremid Genomic Services, tells GEN that the technology, which is still used to generate transgenic plants, is not without challenges, primarily the inability to control where the new genes are inserted once they enter the cell. It helps explain why newer technologies like CRISPR have begun to gain ground both for plant and animal genomes.

Last year, British company Genus developed CRISPR-edited pigs that are resistant to porcine reproductive and respiratory syndrome, which has decimated pig populations. Companies like Elo Life Sciences and Inari are using gene editing techniques to sustainably improve food crops. While Eremid does not provide gene editing services directly, the company works with various agbio partners that do. It provides sequencing services to help its partners assess the outcomes of the editing efforts and ensure that their changes yield the desired phenotypes without damaging the integrity of the plant.

From Curaba’s perspective, one of the primary benefits of editing technologies is the ability to get improved varieties of agricultural products to market much faster than with traditional breeding. The largest bottleneck for agricultural producers is the turnaround time for developing improved varieties with traditional breeding. Gene editing gives scientists “a fast way of creating new varieties of plants,” he says.

CRISPR-based editing fulfills another important purpose. Academic scientists, in particular, are using the technology to better understand gene function and the effects of modifying genes on plant development and specific phenotypes, Curaba notes. That information can then feed into commercial efforts to improve global food systems.

Smart gene editing with AI

When she first came across CRISPR-based editing, Catherine Feuillet, PhD, immediately saw its potential to transform plant breeding. As an expert in the space, she was familiar with the challenges of older editing technologies like TALENs.

“You had to produce a TALEN for every edit you wanted to do so it was not amenable to multiplexing,” she explains to GEN. “You also need to have a specific knowledge and a partner company to help to produce your TALEN.” In contrast, CRISPR editing is cheaper and easier to make and use.

Feuillet is now the chief scientific officer of Inari, a company using gene editing to develop improved seed varieties. Armed with predictive design tools powered by artificial intelligence (AI) and a toolbox of multiplex gene editing capabilities, Inari scientists are working on generating improved varieties of soybean, corn, and wheat for commercial use.

Current breeding practices have been crucial for boosting food production, but it takes years and multiple crosses to identify and cultivate plants with desirable characteristics. Modern sequencing instruments and other advanced technologies have markedly “changed our ability to produce data,” Feuillet says. “We have the capacity to extract a lot of information from this data” and to “really change the way we do breeding.”

Urgent efforts

There is an urgency to these efforts. With threats to agriculture systems from climate change and emerging infections on the rise, food producers can’t wait 10–15 years to get improved crops, Feuillet says. “We need to do these edits, and we need to predict how this improves the characteristic that we are trying to improve. That timeline should be five years maximum.”

Inari’s proprietary platform pairs computational modeling with gene editing to find the best versions of its target crops. On the computational side, Inari has developed AI-based technology to identify gene sequences that are causal to plant performance and to identify ways to edit them to boost preferred traits. The company’s multiplex editing platform lets it edit several genes simultaneously. That’s important because “the big problems in agriculture cannot be addressed by single gene solutions.” Feuillet says, “It’s not enough to knock out the function of a gene or even 10 genes. Multiplexing is about editing several genes at the same time and doing different types of edits.”

Inari chose to work with soybean, corn, and wheat because these have the biggest impact on global agricultural production. The company has made the most progress on developing improved soybean plants with corn as a close second, Feuillet says. The first wave of edits has been focused on increasing plant yield without requiring more input from producers. The next wave of edits will focus on efficient resource use. That means obtaining the same yield from plants using less water and less nitrogen.

Over the last three years, Inari has also invested resources in generating the data needed to train its AI models to filter and rank genes of interest. Plants have significantly larger genomes than humans and there are a lot less data available from plant genomes than there are from human genomes. Inari has hired several scientists who previously worked in drug discovery and Feuillet says they are often surprised at the dearth of data on plant genomes. “Compared to pharma we [don’t] have the same amount of data at all because there is less investment and much less access to it.”

Furthermore, plants have a lot of duplication in their genomes that is not seen in animal genomes. In soybean for instance, which is a palaeopolyploid species, 75 percent of its 50,000 genes have multiple copies.

Besides helping scientists select which genes and combinations of genes to edit, the company is also using its models “to build hypotheses on what the next set of data we need to have to continue to train and fine tune them” as well as what assays they could use to validate their hypotheses.

As with traditional breeding, edited plans also need to undergo field testing to ensure that they have the traits of interest.

“I see CRISPR as an acceleration of breeding and that’s why it’s so important,” Feuillet says. “It’s fantastic that this is applicable both for human therapeutics and for agriculture. It has also opened an opportunity for new players like us to come into an industry that has not seen a lot of new players. I believe that this is here for the long term and it’s starting to change things.”

Rescuing endangered foods crops

Matt DiLeo, PhD, head of R&D at Elo Life Sciences, describes the company’s goal as reimagining the future of food. “The way that we’re approaching this is to unlock nature’s abilities to make consumers’ favorite foods more delicious, healthy, and friendly,” he explained.

Gene editing is one of the tools helping Elo accomplish its mission. Here the company is focused on editing fruits and vegetables with an eye towards preventing the extinction of different fruits and vegetables due to factors like climate change. “There’s many cases where we know exactly what’s holding the plant back, we know the gene that we have to change but when you do this with traditional breeding it takes a very long time,” DiLeo noted.

The power of gene editing is that it is possible to make small changes to the genome and get results quickly.

While some companies in the agbio space have embraced CRISPR-based editing, Elo opted to develop its own proprietary gene. It’s a protein-based technology that uses a gene editing capability. “It’s actually the oldest of all the editing technologies” older than even TALENs and zinc fingers, DiLeo said. “Because it’s protein, you have to have a team that can build [them] it’s not something you can just order online. But it’s sensitive and you can tune it in a way that gives you additional advantages over CRISPR.”

For example, they are able to make edits to address a broader set of traits than may be possible for other technology providers. Additionally, because Elo owns the intellectual property, the company can commercialize its nucleases with whatever terms make the most sense for its partners, something that would be challenging to navigate with CRISPR, especially considering the current patent disputes.

Both of these factors are important to partners like Dole, who tapped Elo to work on a project aimed at creating resistant banana cultivars. The goal was to develop varieties of banana that are resistant to a Tropical race 4 (TR4) deadly fungus that has wiped out banana farms around the world. Banana producers have been scrambling to find varieties capable of resisting the fungus. As it turns out, cultivars of Cavendish bananas have been able to resist the fungus. Cavendish bananas, which are widely sold in North America and Europe, are grown in a small number of Central and South American countries due to the invasive infection. However, producers know that it’s only a matter of time before even those farms are under threat.

That’s why “the big banana companies have partnered up with universities and tech companies to try and find some solution to this problem,” says DiLeo, who is a plant pathologist by training. Working with Dole, Elo used its gene editing approach to make only the small changes to the Cavendish banana’s genome to strengthen its resistance to the fungus. When they started the project in June 2020, Elo’s scientists had not worked with bananas before. To understand just what they were up against, bananas have about 36,000 genes, and unlike humans, scientists have access to much less data on banana genes and their functions.

In the roughly four years since the project began, Elo has designed editing methods for the bananas and “done a deep analysis of all the molecular changes that we could make to bananas to make them resistant,” DiLeo says.

The company has grown its edited bananas in greenhouses and tested them with large inoculations of TR4 to ensure that the edits worked. Now the company is running field trials of the edited bananas in farms in Latin America that test their ability to resist infection.

Besides the banana project, Elo is also applying its gene editing capabilities to other partnerships including a project with a large NGO focused on improving crops like cassava for subsistence farming.

“We really want to have an impact on people’s health and well-being sustainability,” DiLeo said. “Having a clear path where you can do it in a way that is economically viable is really important and there’s a lot of exciting technologies out there. The ones that are going to change the world are going to find a way to make people’s lives better while saving their money.”