In recent years, with the vigorous development of RNAi drug research and development and breakthroughs in related technologies, the research and development of RNA biopesticides has also entered a period of rapid development. At present, Bayer (Monsanto) has achieved remarkable results in the research and development of genetically modified corn (MON87411) and sprayed RNA biopesticide (BioDirect), and has basically achieved commercialization. Syngenta has also achieved results of great commercial value in the use of RNAi technology for pest control. At the same time, some emerging agrochemical companies and a large amount of capital have also joined the ranks of RNA biopesticide development, which has greatly promoted the development and commercialization of RNA biopesticide.
The process of RNA biopesticides from laboratory to market requires technical links such as target discovery, dsRNA production, and dsRNA delivery. Among them, dsRNA is extremely prone to degradation in complex field environments or in the presence of nucleases. Therefore, stable delivery of dsRNA is crucial for the commercialization of RNA biopesticide technology. At present, a number of companies have developed various auxiliaries and nanotechnology research and development specifically for the stability of dsRNA. The representative company, AgroSpheres, is an agricultural biotechnology company located in Charlottesville, Virginia, USA. It has established a biological particle delivery technology platform for the production of RNA biopesticide active ingredients by bacterial fermentation, slowing down dsRNA in the delivery process. Degradation problem, but also has the properties of active ingredient release controllability, enhanced adhesion and other properties.
AgroSpheres, the delivery of active substances
At the heart of AgroSpheres' proprietary AgriCell delivery technology platform is a bioparticle loaded with synthetic chemicals and biologics, which are small spherical biocells (approximately 400 nm) produced during fermentation of parental bacterial cells.
■ Bioparticle production
1) Selection of fermentation chassis: At present, AgroSpheres uses Escherichia coli to produce biological particles, but other rod-shaped bacteria can also be used as fermentation production chassis;
2) Fermentation production process: The biological particles of AgroSpheres are small spherical organisms separated from bacterial mother cells during the fermentation process, which can be mass-produced at low cost. During fermentation, bacterial mother cells separate out small spherical organisms. Because it does not contain chromosomes, the EPA has determined that the bioparticles produced are non-GMO;
3) Active ingredient loading: The loading of exogenous active ingredients (synthetic chemicals and biologicals) is achieved by co-incubating biological particles in a solution containing active ingredients.
■ Bioparticle properties
1) Protection of active ingredients: Bioparticles can protect the encapsulated active ingredients from extreme temperatures, pH and environmental chemicals ribonucleic acid (dsRNA) is protected from environmental ribonucleases and hydrolysis;
2) Control the release of active ingredients: The release kinetics of the active can be regulated during the production of bioparticles. For example, the addition of agents that cross-link bioparticle membranes resulted in stronger membranes, which slowed the release of coated actives, even for up to two months;
3) Enhanced adhesion: Another key feature of bioparticles is the ability to embed proteins on their membranes. Proteins like carbohydrate-binding modules enable bioparticles to stick firmly to plant leaves, preventing rain from scouring, and the proteins can also be used to target specific pests.
The perfect entrepreneurial ecology supports the business path combining AgroSpheres technology platform and product development
AgroSpheres is positioned in the synthetic chemical pesticides and biological pesticides market, and it not only attaches importance to cooperation, but also has its own product research and development. Since its inception, AgroSpheres has successfully secured financing from multiple investors, partnering with target customers including companies that require advanced formulation technologies for more efficient delivery of active ingredients, while AgroSpheres is also focusing on developing its own pesticides and fungicides and sell to growers through channel partners.
AgroSpheres, partner company
1) In 2020, AgroSpheres entered into a strategic alliance with Orion Integrated Biosciences, a leading company in the field of algorithmic technology to identify specific genomic regions, and Orion generated new, hyperspecific RNAi targets for AgroSpheres' crop protection product portfolio. AgroSpheres provides Orion with access to the AgriCell platform to manufacture and formulate products for biodefense and animal health applications;
2) AgroSpheres signed cooperation agreements with GreenLight Biosciences and TechAccel to study the encapsulation of double-stranded ribonucleic acid (dsRNA) and to test the transmission efficiency of double-stranded ribonucleic acid (dsRNA) for controlling Colorado potato beetles and lepidopterans;
3) In 2022, AgroSpheres entered into a new model partnership with Bayer to develop novel biologics for use as crop protection products using AgroSpheres' AgriCell system.
4) According to public information, the layout of AgroSpheres' RNAi-based crop protection biological product pipeline currently mainly includes an encapsulated RNAi product and a biological fungicide that are in the development stage for the control of Spodoptera frugiperda larvae.
■ A good innovation and entrepreneurship incubation ecology paves the way for AgroSpheres growth financing
The good innovation and entrepreneurship incubation ecology overseas is worthy of the domestic industry's attention and reference. After reviewing the growth process of AgroSpheres, we can find that the innovation and entrepreneurship capital support not only provides key support for the start-up stage of AgroSpheres, but also lays the foundation for its subsequent smooth financing:
1) In August 2017, AgroSpheres completed a seed round of financing of $750,000. Before that, they have won a total of 174,000 US dollars in prizes by participating in various innovation competitions, helping the company to smoothly advance its R&D plan in the start-up stage, and bringing the results of the laboratory to the field validation stage;
2) In 2019, Virginia Catalyst announced a $600,000 award to AgroSpheres, accelerating the company's pace of entry to the market and significantly improving its ability to attract more investment;
3) In 2019, AgroSpheres received a $225,000 grant from the National Science Foundation Small Business Technology Transfer to conduct research and development (R&D) work on RNAi bioinsecticides against Western flower thrips;
4) In 2019, AgroSpheres received USD 4.5 million in Series A investment, led by Ospraie Ag Science, with participation from precision agriculture leader Wilbur-Ellis. In September 2020, AgroSpheres announced an increase in Series A funding to $8.8 million. These investments will primarily be used to drive the commercialization of its products;
5) In 2019 AgroSpheres received US$75,000 from the Centre for Innovative Technologies (CIT) and the Commonwealth Research Commercialisation Fund (CRCF).
The bioparticles of AgroSpheres can be obtained by means of engineered fermentation, thus enabling large-scale production at low cost. From the perspective of market prospects, the research and development results of AgroSpheres have good ductility and can be used not only for the development of chemical and biological pesticide formulations, but also for fertilizers, veterinary drugs, medicine and other fields, with great potential for development. More overseas companies dedicated to the research and development of dsRNA delivery include: NanoSUR has developed a proprietary platform to modify dsRNA into MdsRNA through a certain coating to improve transmembrane efficiency and slow down degradation; Trillium Ag has developed Agrisomes agricultural biological platform, which can modify dsRNA by modifying dsRNA. Assembled to improve dsRNA targeting, specificity, and delivery efficiency. Domestic companies such as Zhisheng Yougu, Xiaomo Bio, and Silicon Yi Technology have also continued to promote the research and development of dsRNAd delivery, thereby accelerating the commercialization of the domestic track.