Genome editing with CRISPR and other tools is an exciting new technology with myriad applications from human health to industrial biotechnology. Gene editing allows small but precise changes in DNA sequences to turn genes on or off or modulate their activity. It is an extremely active area for investment, particularly since the announcement of the first CRISPR-based human gene therapy approval November of 2023. Editing technology also has tremendous potential for applications in agriculture and this week there was an announcement of a new partnership between a major global agriculture company, Corteva, and a genome editing company called Pairwise. This sort of development and innovation is important because the global agricultural sector faces many challenges and opportunities including:
- Feeding a growing global population without encroaching on remaining wild lands
- Growing crops in an environment that increasingly involves more heat and water stress events driven by climate change
- Striving to reduce the carbon footprint of farming while also aiding footprint reductions for other industries such as animal production, fuels and plastics
- Playing a positive role in net global carbon sequestration
- Managing new and intensified pest challenges driven by pesticide resistance and climate shifts
- Creating crops with novel consumer-oriented characteristics to enhance food enjoyment and health
Fortunately, these challenges are being addressed through extensive efforts by both public and private R&D entities. One current example involves Corteva, a global agricultural technology company that merged the resources of Dow Agrisciences, DuPont and Pioneer. In March of 2024 Corteva announced the establishment of an investment and partnership platform called Catalyst with the goal of connecting its own resources and expertise with entrepreneurs and other innovators.
On September 17, Corteva announced a $25MM equity position and separately funded joint venture announced on September 17th working with a company based in the North Carolina Research Triangle called Pairwise, which also is at the cutting edge of genome editing technology. This was the first joint venture and major equity investment in gene editing by Corteva via Catalyst. The new relationship has the promise of taking Corteva’s existing crop breeding and gene editing programs to a new level through the synergies that occur when pairing editing tools with the other resources, experience and advanced technologies already in Corteva’s breeding toolbox and ultimately through their marketing channels. Gene editing has potential uses for many traits in crops, but particularly stress tolerance, disease resistance, altered dormancy patterns, modified crop architecture, and also for creating consumer-oriented traits.
For its own business, Pairwise has focused on specialty crops and in 2023 released Pairwise-edited leafy greens; the first approved, gene edited food crop – the first CRISPR food introduced in North America (Image via Pairwise) – a leafy salad vegetable mix without the bitter taste that inhibits many consumers from choosing this healthy option. The Pairwise development pipeline also includes cherries without pits and blackberries without hard seeds (which are technically also pits). For these crops it is usually possible to start with a short list of desirable cultivars, but one of the harder steps is working out a regeneration protocol to go from individual edited cells through a tissue culture step to regenerate whole plants.
As Pairwise worked on its projects it has developed a sophisticated suite of proprietary gene editing methods which they call their Fulcrum™ Platform. That toolbox addition is of great interest to a company like Corteva that mainly works with multi-million acre row/commodity crops like corn and soybeans.
Corteva and its main competitors such as Bayer, BASF and Syngenta have advanced crop improvement capabilities based on extensive libraries of elite breeding lines that are specifically adapted to each of the growing environments and/or commodity sub-categories they serve. They are then able to carry out the steps of “conventional breeding” with enhanced efficiency using a technology called Marker Assisted Breeding (MAB). Standard breeding and hybridization involves generating the vast range of variation that occurs with the random mixing and matching of thousands of genes. By doing a DNA test on a tiny piece of each new seed from a cross, these breeders can identify the small subset of seeds that have the most of a list of highly desirable genes so that only those need to be grown out in the field to see which are the best candidates either for additional breeding or for moving into commercial production. This is still the widely accepted process of “conventional breeding” from a regulatory and downstream market perspective, but it can also be used to sort through candidate seeds that come from edited lines. The single-cell-to-plant step for corn and soybeans has already been worked out for the transgenic improvements typically called “GMO.” This is different from gene editing, which is non-transgenic, and so there will be immediate synergy between the Fulcrum™ Platform tools from Pairwise and the MAB tools of a Corteva. Bayer Crop Science, another global agtech player, last year entered into a new five-year, multi-million dollar agreement with Pairwise. This second collaboration between the two companies is focused on innovations in short-stature corn.
The regulatory pathway for genome edited crops is still evolving and that trajectory is being tracked at this independent, informational site. The US is in the process of finalizing it’s regulatory system for gene edited crops.
In an interview for this article, Sam Eathington, the Chief Technology and Digital Officer for Corteva expressed confidence that the result will be a much less convoluted system than that which applies to transgenic crops. This is because the results with editing are analogous to what occurs during conventional breeding and does not involve “foreign genes. Therefore, Eathington is optimistic that the technological and resource synergies of the Corteva/Pairwise partnership will result in valuable tools for modern agriculture in the not-too-distant future.
Brazil and New Zealand are also well along in implementation of a practical regime, England may follow suit. An active debate continues within the EU and it is not yet clear what rules will be set up for imports and whether or not they will ever allow their own farmers to benefit from this technology. For crops like corn and soybeans the lack of international regulatory harmonization has not prevented extensive adoption of transgenic technology in the US, South America, Canada and many other countries and this scenario is expected to extend to gene edited versions of those crops.
A company in Argentina called Bioceres Crop Solutions Corp has developed a gene edited wheat with enhanced stress tolerance and herbicide tolerance so it will be interesting to see if that crop will ever overcome the regulatory and market barriers that have kept most wheat breeders from being able to utilize many modern genetic technologies.
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