From Bio Journal - November 2023

Trend: Spreading use of RNA backed up by the Nobel Prize

DNA manipulation used to be the dominant technique In genetic engineering, but RNA manipulation is currently becoming more widespread. This is symbolized by the Nobel Prize. On October 2, University of Pennsylvania professors Katalin Karicó and Drew Weissman, who developed a messenger RNA (mRNA) vaccine, were named winners of this year's Nobel Prize in Physiology or Medicine. Traditionally, it has taken a considerable amount of time to decide on a winner after the results have been evaluated. In recent years, however, there has been a tendency to decide on the winner before the assessment is fully established. This is what happened with iPS cells, and also CRISPR-Cas9. That's what happened with the winning of the Nobel Prize with this mRNA vaccine, which is the COVID-19 vaccine. RNA technology is in its infancy, and it may be dangerous if it is used in the wrong way.

The full-scale use of RNA began with the creation of genetically modified crops using RNA interference (RNAi). RNAi is a technique that blocks the action of specific genes it targets. The way genes work is that genetic information in DNA is copied into mRNA. Amino acids are then linked together based on the information transcribed onto the mRNA, and the linked amino acids are proteins. This is the basic flow of genetic information, but RNAi uses processed RNA to interfere with genetic information at the mRNA stage.

Potatoes developed using RNAi were grown in the United States and approved for distribution in Japan in 2017. The potato was developed by Simplot, which reduced acrylamide, a carcinogen produced when heated. Later, a trait that reduced the blackening by bruises when potatoes hit hard objects was added and also approved.

In RNAi, a dsRNA (double-stranded RNA) that has an RNA structure complementary to the mRNA you want to inhibit, is produced for the gene that is to be blocked. Complementary means the RNA snap together to form double-stranded RNA. When the artificially produced dsRNA enters a cell, an enzyme converts it into single-stranded RNA (siRNA). The siRNA snaps onto the mRNA. When double-stranded, the mRNA loses its function and disassembles, resulting in the cessation of gene activity. The ease with which genes could be turned off led to wider applications.

Furthermore, the spread of mRNA vaccines for COVID-19 has dramatically expanded the use of RNA. Previous vaccines have used viruses, such as attenuated viruses, or parts of viruses. The mRNA vaccine is a lipid nanoparticle wrapped around the mRNA that makes the coronavirus spike protein. mRNA is artificially synthesized. The spike protein is the part of the protrusion around the virus that acts as an antigen and triggers antibodies. The principle is that the vaccine effect is exerted through the formation of antibodies, so that even if a person is infected with a virus, he or she is already prepared to attack the virus.

The features of mRNA are that it is easy to synthesize, easy to develop various types, and is easily mass-produced. That is why the method will be used to develop and manufacture other vaccines, such as the flu vaccine, increasing the likelihood that it will become the mainstream vaccine production method. It uses large amounts of mRNA wrapped in millions or tens of millions of lipid nanoparticles, making it easy to include several different vaccines. The development of vaccines for use in animals is also about to get underway.

Agrochemicals are getting the most attention, with chemical manufacturers developing RNA insecticide and herbicide alternatives to traditional agrochemicals. These agrochemicals also use RNAi. Companies such as Bayer, BASF and Syngenta have already developed insecticides that target the Colorado potato beetle.

When used in insecticides, the RNAi are designed to activate apoptosis (sudden death) genes. What is destroyed is a gene called an apoptosis inhibitor, important for preventing sudden death. Destroying the gene causes sudden death and the chemical thus functions as a pesticide. Facile expansion of use of the pesticide risks setting off a major biological disaster that can never be reversed. The use of RNA has only just begun, and the potential danger is huge. There is a concern that endorsing this technology by awarding the Nobel Prize to its inventors will encourage the facile expansion of applications.

Shizuoka Prefectural Assembly passes resolution calling for first genome-edited food labeling

On October 13, the Shizuoka Prefectural Assembly passed and adopted a "written opinion calling for consideration of how information should be provided to consumers, including the labeling of food products applying genome-editing technology." This is the first time a local government council has passed a resolution calling for the labeling of genome-edited foods. The documents will be submitted to seven locations, including the chairmen of both houses of the Japanese parliament and the prime minister. In the past, when genetically modified food began to be distributed without labels, the Tokyo Metropolitan Government adopted the first resolution, with local assemblies across the country following suit, sending 1078 letters to the Minister of Agriculture, Forestry and Fisheries (MAFF) and 1224 to the Minister of Health and Welfare (now MHLW).

Iwata City becomes major base for land-based fish and seafood farming

NTT Green & Food, a joint venture of Regional Fish Institute Ltd., which is developing genome-edited fish, and NTT, will conduct onshore shrimp farming on the site of a former factory owned by a subsidiary of Suzuki Motor Corp. in Iwata City, Shizuoka Prefecture. The plant, expected to produce about an annual 100 tons of shrimp, is scheduled to start operation around summer 2024. Regional Fish has already commercialized a genome-edited tiger puffer and red sea bream, and is currently developing a genome-edited whiteleg shrimp (Litopenaeus vannamei). As NTT has been developing algae to feed fish and shellfish, this enterprise appears to be a combined effort. A Kansai Electric Power Co. subsidiary, Kaiko Yukinoya, opened a new large-scale onshore whiteleg shrimp farming facility in Iwata City last July, and the area is likely to become a major onshore aquaculture zone. In addition, Regional Fish also has an aquaculture farm on the premises of Kansai Electric Power Co., Inc. in Miyazu City, Kyoto Prefecture, and can be said to be strengthening its cooperation with Kansai Electric Power and NTT.
(Shizuoka Newspaper 2023/10/11, and others)

US synthetic biology pioneer files for bankruptcy

The synthetic biology company Amyris, Inc. filed for bankruptcy on August 9. Synthetic biology is a field of research and development in which organisms are artificially synthesized and created. Since the company was at the vanguard of the field, there will inevitably be impacts on companies of this type going forward.
(Nikkei Biotech Online Version 2023/9/27)

Biostimulant company gets underway

AGRI SMILE, a Tokyo-based company that is developing biostimulant technology, one of the pillars of the Green Food System strategy promoted by the Ministry of Agriculture, Forestry and Fisheries, has started up in earnest. Biostimulation is a technology that increases the immunity of plants and is said to be a biological stimulant. Although biostimulants do not directly nourish plants, they aim to make them more resistant to adverse environments, e.g. through developing stronger roots, and thus become the third agricultural material after agrochemicals and fertilizers. On September 7, the company jointly established the Council for Regional Decarbonization Using Biostimulants.
(Nikkei Biotech Online 2023/9/19)

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