The past 10 years have seen incredible advances in CRISPR thanks to massive private and public investment. Yet has the technology already fully revealed its potential? And what can we expect in the future? These are the big questions Gusui Wu, Head of Seed Research at Syngenta, addressed in his presentation at World Agri-Tech in San Francisco on March 20.
“In the last decade, depending on…how you do your math, somewhere between four and six billion dollars has been invested in start-ups that are applying CRISPR to agriculture. About the same amount of dollars or more has been invested by large and small seed companies to edit genes in crops. Substantial public sector investment or funding has been made in plant gene editing research. As of January, there were 53 USDA exemptions for gene-edited traits in about 17 crops,” he said in his presentation.
Still, he pointed out, large-scale delivery of CRISPR-influenced products has yet to occur. It could even be argued that indicators of investor enthusiasm are waning.
“It’s probably fair to say that we haven’t seen such a high-impact, large-scale commercialization of gene-edited products in the marketplace. And venture funding has slowed in the last few years in gene editing in agriculture,” he said.
The question is: do we still believe that CRISPR is a disruptive, revolutionary technology that could lead to new breeding technologies? Do we still believe that CRISPR technology is a good investment opportunity that can make the harvest of the future happen?
Wu didn’t hesitate for a moment about his answer: “From Syngenta’s point of view, the answer is yes.”
To understand today’s reality of gene editing technology and use, Wu said we need to look at the latest disruptive, revolutionary technology in plant breeding: transgenic technology for genetically modified traits. This technology was first published in 1983 by Syngenta scientist Mary-Dell Chilton, but the first transgenic trait was not commercialized until 1996. Why such a delay? The regulatory process is certainly part of the story, but not the whole story. Wu said the reason it took more than 10 years was the fact that the plant transformation technique, as revolutionary as it was, was not enough on its own to build a transgenic trait.
“To successfully build a transgenic business, you certainly need plant transformation, but a number of related application technologies were needed [as well].”
In the case of transgenic traits, related technologies include trait genetic engineering, plant expression tools, and trait introgression technologies to introduce traits into elite hybrid varieties.
The delay in uptake and commercial application of CRISPR is similar.
“The CRISPR technology itself is not a new breeding technology. Let’s get this straight. It’s just a tool that allows for a lot of breeding technologies that can happen,” Wu said.
The good news, he added, is that there has been significant progress over the past few years in making CRISPR technology the next step, which would allow new breeding technologies to emerge. He shared some examples from the Syngenta team that illustrate that CRISPR is finally reaching the tipping point needed for true commercialization.
The first significant signpost is the diversification of CRISPR-Cas systems.
“Cas9 is effective but has many limitations. We need diversified CRISPR-Cas systems for new breeding technology to happen,” he said.
Already, a number of companies — Wu mentioned Pairwise — have developed alternative CRISPR systems. Syngenta has developed a Cas12-based system that is just as effective as Cas9, but overcomes many of Cas9’s limitations, including what Wu called its dark IP pathway.
“Traits can be developed with gene editing today with current technology if those edits are simple,” Wu said.
For example, Syngenta is currently working on several key traits, including extended shelf life and disease resistance in tomatoes and rust resistance in Asian soybeans.
“We see many new features in development being developed by various entities, public and private. There is a democratization of technology that is different from [how] GM technology has come along in the last few decades, which is a good thing,” Wu said.
The second area of remarkable opportunity, which is still largely overlooked, is that CRISPR can improve the efficiency of the breeding process.
“It was not widely appreciated,” Wu said.
For example, when gene-editing technology is combined in one step with a hybrid breeding process called the doubled haploid technique, then applied to trait introgression, it reduces the time for trait introgression from six or seven generations to one.
“With one cross, you can introduce the trait into all the elite varieties or hybrids you want,” Wu said.
Perhaps the biggest opportunity before CRISPR is how gene editing can be applied to complex traits where you need complex, multiple gene modifications or pathways.
“It could happen today; we see the opportunity and the potential,” Wu said. “With gene editing combined with machine learning, now even artificial intelligence, we can now create engineered genetic variations. Variations can give you highly predictable results, and today we see examples demonstrating this. So this opportunity is going to be huge.”
The next stage for CRISPR is likely to be the most exciting and the opportunity to have the biggest impact on the market.
“I hope we have passed the stages of inflated expectations or the troughs of disappointment and entered the stage of enlightenment,” Wu said. “From an investor perspective, we have to remain optimistic about the next five or the next 10 years in terms of innovation and investment opportunities.”
