Leveraging CRISPR gene editing capabilities and a proprietary global microbial database, AgBiome pursues agtech and life science breakthroughs.

Research Triangle Park firm is creating a pipeline of promising biotech innovations by cataloging millions of microbes and modifying their gene sequences

In the world of technology-driven companies, the core value by which they are measured often resides in their Intellectual Property (IP). For most entities this takes the form of copyrights, patents, industrial processes, programming code, trademarks, and trade secrets. The researchers at AgBiome, a biotech firm in Research Triangle Park, NC, are creating value for their investors, and the scientists and farmers of the world, in an entirely new manner – literally one microbe at a time.

Founded in 2012 and well-funded by a consortium of topline venture capital firms and biotech heavyweights, AgBiome is creating a “biological portfolio” of diverse microbes gathered from across the globe. This Noah’s Ark of sequenced microbial strains, stored in their proprietary Genesis gene and strain identification system, provides their scientists with a rich pool of genomes to draw from for their research. The goal is simple but the path to success often complex: editing the DNA of microorganisms and proteins to optimize their ability to kill pests, fungal pathogens, weeds, and other forms of blight.

With one of the world’s largest collections of sequenced microbial strains at their disposal, (45,000 strains and growing at 15,000 per year), the company says their proprietary bioinformatic analysis capabilities will yield a flood of commercial applications. Recent scientific breakthroughs in genetic engineering also fortuitously provide AgBiome with a highly efficient toolset to streamline the challenges at hand. Unlike earlier biotechnology companies which relied on time-consuming and costly GMO (Genetic Modified Organism) genetic alteration techniques, AgBiome scientists have the benefit of CRISPR, an extremely precise and cost-efficient genome editing technique called CRISPR. Developed over the past decade by researchers the world over largely working independently of each other, CRISPR is revolutionizing all aspects of biotechnology research and life sciences in general.

How CRISPR Works and Why It’s Changing Everything

When microscopic organisms, or microbes, are invaded by a virus, their natural defensive response is to capture the DNA of the invader and use it as a weapon. All single-celled organisms accomplish this by inserting DNA sequences acquired from previous viral infections into the DNA of the current threat, literally “cutting” it’s DNA apart. Although “adaptive immunity” was recognized as a universal way most living things deal with disease (it’s why humans began to develop vaccinations), the precise way bacteria accomplished this was not fully understood.

Then in 1987 scientists at Osaka University uncovered a clue about how this process works. During a cloning experiment using E. coli bacteria they noticed clustered DNA repeats, or sections of “spacers” in the DNA strands that had resulted from their experiment. Although they didn’t know it at the time, they had stumbled upon the fundamental mechanism single-cell microbes use to edit genes.

Further research by scientists at the University of Alicante in Spain identified the proteins involved in the process. In their peer-reviewed paper, the Spanish researchers suggested naming these unexpected DNA sequencing CRISPR, for clustered regularly interspaced short palindromic repeats. They also named the proteins key to this process “Cas” proteins (CRISPR associated systems).

Over the past decade, scientists have determined that CRISPRs, or DNA sequences with repeating spacers and direct repeats, occur in most bacteria and archaea, the two primary unicell organisms found in nature. While other techniques to edit and manipulate genes have existed for several years, the implications of being able to precisely edit the genome of a living cell efficiently, in mass quantities, and at an extremely low cost, are immense.

Breakthroughs are already occurring across virtually all of the forms of scientific research. CRISPR genome editing is currently being used in life sciences, agtech, and other endeavors which involved the editing of genes. In simple terms this means it’s now possible to remove undesirable traits from genes and insert beneficial characteristic in any plant, animal, or even in humans. Although CRISPR provides scientists with powerful new capabilities, regulators, academics, bioethicists, and research governing organizations warn that tampering with DNA has the potential to unleash a Pandora’s Box of unintended consequences. The first known case of human gene editing has proved this worry to be well founded.

Last autumn Chinese scientist He Jiankui announced that he had modified the DNA of an embryo which produced twin girls. His intent was to make them resistant to the HIV virus, a disease which still poses a public health threat in much of China. Shortly after publishing his study, he admitted the editing did not go as planned. Further analysis by other scientists now indicate the girls may be at greater risk from other viruses such as West Nile and influenza. Even more troubling was the results of an analysis of over 400,000 people with the same mutation as the girls which showed the girls were 21% less likely to live to the age of 71 than the general population.

Many in the scientific community point out that making changes in human embryos poses serious risks, both immediate and long term. Genetic mutations, they argue, will likely be inherited by future generations and could create a ripple effect across the entire human gene pool. Clearly, the moral dilemmas and ethical ramifications are significant and will persist indefinitely.

Ambitions Beyond Agtech

Already a shining star of the agtech world, AgBiome has garnered the support of biotech leaders Bayer, Novozymes, and Syngenta, all of whom have provided funding. The products emerging from AgBiome for the agricultural markets are being commercialized by its AgBiome Innovations subsidiary, a division charged with licensing both its agtech and human therapeutic intellectual property. The first products to hit the market are all biopesticides, a broad category of crop treatment substances which include fungicides and insecticides derived from natural organisms to combat common crop diseases and pathogens.

A sign of the real-world applications of its research was evidenced by a research grant from the Bill & Melinda Gates Foundation last summer.  The multi-year funding will support LifeEDIT’s study of roundworms, tiny microscopic parasites which devastate the yam crops of African farmers. In addition to fulfilling the humanitarian promise of genetics, it certainly also provides a showcase for the practical application of AgBiome’s claim to be capable of  “targeting of any gene in any position” to achieve desirable outcomes.

Newly Spun Off from DuPontDow, Corteva Agriscience Plans to Grow Up Quickly  

Existing genetically modified seed expertise will be enhanced significantly with CRISPR-Cas9 gene editing technologies.

Almost two years ago, on August 31, 2017, Dow Chemical, the 127-year old chemical producer merged with the 217-year old EI DuPont de Nemours. The combined powerhouse, DowDuPont created the biggest chemical entity in the world with $86 billion in annual sales. Now, just 17 months later, DowDuPont is spinning itself off into three separate companies. Dow is already again trading under its own stock symbol and DuPont will follow shortly. Owners of DowDuPont stock will end up owning stock in all three new securities and likely see roughly the same dividends, although in three separate checks.

The new face on the “big board” will be Corteva Agriscience, a name that didn’t exist before DowDuPont announced it in February 2018. The new entity is essentially a re-branding of the assets of the DowDuPont agricultural businesses and the products and facilities of Pioneer Hybrid International. Founded in 1926 in Des Moines, Iowa, Pioneer was a leading producer of hybrid seeds and genetically modified seeds when it was purchased by DuPont in 1999. In light of the high profile multi-billion acquisitions in the agtech sector (Bayer AG’s purchase of Monsanto, Syngenta’s sale to China National Chemical, and the DowDuPont merger itself), clearly the hope is Corteva will grow its market value quickly.  

With revenue of just over $14 billion last year, Corteva will seek to gain cost savings by eliminating employees and operational overlap. Management is planning to reduce overhead by $1.2 billion through “cost synergies”, which usually means job eliminations. However, to date only a handful of layoffs have occurred, despite fears of a headquarters move from Indianapolis, Ind. To ensure the company would stay put, the City of Indianapolis paid a $30 million “cash incentive” in a deal that would keep a minimum of 1,254 of the 1,400 person workforce at the company’s headquarters. The deal was received with a mixture of relief and controversy, especially among residents who reminded city council members that parent DowDuPont had never even implied a Corteva departure.

DowDuPont officials say Corteva will maximize its market share and as a global pure-play agricultural company. The majority of its products and research will continue to be the production of pesticides, herbicides, and fungicides, in addition to its considerable Pioneer seed division. Most of Pioneer’s business focus was on corn and soybean seeds, selling a variety of hybrid seed corn to nearly 70 countries worldwide. Among the developments which will undoubtedly gain the most attention from investors and agtech competitors will be Corteva’s

use of CRISPR gene editing technology. As a major license holder of foundational CRISPR-Cas9 intellectual property, along with the Broad Institute of MIT and Harvard, Corteva wields significant clout, having the power to grant licenses and enter into joint ventures. In October 17, the Broad Institute and the then DuPont Pioneer announced they would jointly issue free non-exclusive licenses of the foundational CRISPR-Cas9 intellectual property to universities and nonprofits for academic research.

Last August, they jointly stuck a deal to issue a non-exclusive license to J.R. Simplot, one of the largest potato processors in North America. Then, just a month ago, a San Francisco-based startup, Amfora, made a similar deal to develop crops with increased protein content. With the ability to act as a licensor of CRISPR-Cas 9 independently of the Broad Institute, similar licensing arrangements are a certainty, providing further potential upside for Corteva and new revenue streams.

Perhaps tellingly, most significant joint venture to date is its collaboration with the Chinese Academy of Agricultural Sciences (CAAS). A memorandum of understanding (MOU) signed in March of this year to further expand the use of CRISPR potentially opens up a new Asian market of 200 million farming households and 425 million agriculture workers, roughly 35% of China’s total workforce.

In making the announcement, James Collins, CEO of Corteva Agriscience stated that the agreement was a “win-win for the development of agricultural technology and skill development in China. We are committed to enriching farmers’ lives and progressing the ag-industry in China, the expansion of the CAAS-Corteva partnership is a part of our efforts to bring our commitment to life.”