CRISPRが人間の健康を超えて：遺伝子編集の新たな投資フロンティア

CRISPRが人間の健康を超えて

A lot can be said about the amazing capability of CRISPR gene editing for human health. This is something that we discussed in previous articles:

Leading gene editing companies comparisons:

• 遺伝子編集: CRISPR Therapeutics vs. Beam Therapeutics
• CRISPR Therapeutics vs Editas Medicine

Leading genomic tools manufacturers comparison:

Illumina vs Pacific Bioscience: 次世代ゲノムシーケンシング企業の選び方

However, there is no technical reason for gene editing to be confined to humans. CRISPR is already being deployed for new applications like synthetic biology and is even considered for algal biofuels. Still, the largest market beyond human medicine is just getting started: 農業と食品生産のための遺伝子編集.

遺伝子と農業

For most people, the idea of genetic modification and farming brings forth the idea of GMOs. While mostly accepted in some parts of the world, they are strictly banned in other large markets like the EU.

This is a rather limited perspective on the link between genetics and farming. In fact, even the earliest efforts at farming relied heavily upon modifying wild varieties and turning them into “domesticated” breeds. And this was true for both plants and animals.

The first method was selective breeding. Farmers could not create mutations, but they could keep them and spread them when they randomly occurred. They also actively crossed the genetics of different varieties to create more robust, productive, or healthy crops and flocks.

In the 1920s, mutation breeding became a thing. It relies on chemical or radioactive mutagens to accelerate the mutation process and an advanced selection process to find new varieties or traits. Please take note this method is NOT considered GMO and represents the large majority of the food we eat today.

Then, in the 1980s, transgenic breeding started, with foreign genes inserted into plants and sometimes animals. This is what people know as GMOs. Instead of random mutation, the process was a lot more targeted. Still, some details were not controlled, like the location of the inserted gene.

With the first proof-of-concept in the 2000s, we are now getting into genome editing, which might prove the final frontier of crop improvement.

出典: Innovative Genomics

植物と動物の遺伝子編集

We mentioned GMO plants, but this is only one of the best-known applications of genetic modifications.  In modern medicine, anti-blood-clotting protein is produced in goat milk, insulin in GMO bacteria, and other drugs for cancer or multiple sclerosis can be produced in eggs.

Because GMOs are tightly regulated, gene editing might have a huge commercial advantage. According to most regulations, “If it is used to edit the DNA that a plant naturally has, the resulting plant is not transgenic/GM. If it is used to add DNA from a different species, then the resulting plant is transgenic/GM.”

So, many gene editing companies focused on plants or animals could see massive markets like the EU open to them while their traditional GMO competitors are barred from entry.

The potential for CRISPR gene editing in the field is enormous. There are so many possible applications that even just listing them takes a lot of space:

動物

• 脆弱性の低減: サーモン、豚、ウシ、鶏などの疾病。
• 収量の増加: 筋肉量増加、成長速度向上、死亡率低減（例：養殖サーモンの40％が成魚に達しない）。

植物

• 環境条件への耐性向上: 塩分、干ばつ、極端な高温、洪水、風、寒冷・霜。
• 生産性の向上: 光合成の改善、穀物や果実の成熟速度向上、バイオ燃料や堆肥などのバイオマス増加、等。
• 害虫・病害への耐性: 細菌、ウイルス、真菌、昆虫。
• 商業的特性の向上: キノコや果実の変色防止、保存期間と栄養価の向上、種なし果実、色・外観・味の変更、等。

農業の新たな活用

• 植物や動物を「バイオファクトリー」に変えるため:
• ヒト医療: 抗体、医療治療等…
• ヒトへの移植用臓器
• バイオ燃料。
• 香辛料、香料、着色料。
• 非アレルギー性品種。

For a deeper dive into the possibility and challenge of agricultural CRISPR gene editing, Innovative Genomics Instituteのこのページをご参照ください.

CRISPRを農業に活用する企業の選択

Many companies are actively leveraging CRISPR for agriculture, with many already having products soon to reach markets, waiting for the regulators’ approval.

Luckily for the companies working in this sector, the regulatory burden on gene editing compared to traditional GMO is much lighter, according to the prestigious publication Nature: “This has reduced the US regulatory burden for genome-edited plants to next to nothing. Brazil, Argentina, and Australia have taken a similar approach.” The lighter-than-normal regulations in massive agriculture powers like the US and South America offer a large market for gene-edited crops and farm animals, irrespective of the EU decisions and possible change of mind on the matter.

1. Aquabounty

While not technically a gene editing company, Aquabounty pioneered GMO salmon for 30 years.

AQB 価格チャート

Nevertheless, as it is already FDA-approved, it was worth pointing it out to interested investors. Its technology relies on older gene modification techniques but has been studied and proven to be high quality, with no problem from the gene insertion.

2. Bayer

One of the world’s largest biotech and seed companies, after its merger with Monsanto. It controls most of the traditional GMO seed market and is also working on using CRISPR for the next generation of seeds for corn, soybean, wheat, etc.

One part of this effort to evolve from traditional GMOs is done through a partnership with Gingko Bioworks (DNA), one of the largest synthetic biology companies. The partnership is focused on developing biological alternatives to chemical fertilizers via gene editing of microorganisms.

3. Gingko Bioworks

Speaking of Gingko, they are also working on specific options to “farm” bacteria. Notably to replace cannabis plant cultivation with lab-grown cannabinoids.

DNA 価格チャート

It is likely that over time, “farming” for a large array of products like cannabis, tobacco, or even coffee might become a biotech venture more than just growing plants. They are also developing solutions for animal and crop health.

4. Corteva Agrisciences

The $41B company is developing a new line of crops using CRISPR technology.

CTVA 価格チャート

To do so, it leverages a large network of partnerships with international research institutes. It also signed an agreement with French seed producer Vilmorin & Cie for access to Corteva’s CRISPR patents.

5. Benson Hill

When discussing innovation in CRISPR, the focus is often on medical biotech companies or public research institutes. But agribusinesses are also involved in fundamental research, as illustrated by Benson Hill’s discoveries on Cas12a2 and the so-called CRISPR 3.0 discoveries.

The company is focused on soybeans, with also a presence in peas and aquaculture. It is still in the early stages and plans to reach profitability in both EBITDA and free cash flow by 2025.

6. Cibus

The company is modifying plant cells through gene editing and other methods to create bioreactors.

CBUS 価格チャート

These bioreactors can be used to produce molecules used in cosmetics, food, or pharmaceutics. The bioreactors function like cell cultures, imitating how plant tissues are organized, allowing for the production of multiple compounds at once and lower costs.

7. ToolGen (199800.KQ)

The company is using a CRISPR-Cas9 platform for gene editing. It is used for human health, to improve animal and plant traits, and to produce high-value compounds in animal and plant cell lines. Its agriculture research pipeline includes things like soybeans with more healthy lipid content, herbicide resistance, drought tolerance, and pest resistance.

8. Private companies

Not all companies using CRISPR for improving agriculture are publicly traded. Among private companies, startups, and potential competitors to the companies mentioned above, we can highlight Pairwise, Hudson River Biotechnology, PlantEdit, or Inari.