Life is diverse. Spanning from the plant and animal kingdom to infectious diseases, each organism is neatly ordered into its own taxonomic classification. And, despite a general reduction in biodiversity, we are able differentiate between forms of life. This diversity, however, obfuscates the molecular level, which distills living organisms into three, much smaller components: DNA, RNA, and protein. In the late 1950s, Dr. Francis Crick named the directional flow of information from DNA to RNA to protein as the Central Dogma of Molecular Biology – meaning that the flow of information from nucleotide to protein is irreversible. Since then, the private sector and academic institutions have been striving for considerable innovation across medicine, agriculture, and other sectors.
Today across many industries there is a trend towards, and preference for, biological technologies and solutions. McKinsey, the global strategy consultancy firm, outlined four areas of possible innovation: biomolecules, biosystems, biomachine interfaces, and biocomputing. Examples of each area below:
Biomolecules: Gene therapy for personalized medicine
Biosystems: Cultured meat that is created in a lab
Biomachine interfaces: Neuroprosthetic limbs connected to their user’s nerves, muscles, and skeleton
Biocomputing: Building computers and related components, such as data storage, using biological materials or materials that mimic biological organisms (e.g., data storage in strands of DNA)
Here at S2G our focus is investing in food and agriculture companies that make a positive contribution to human and planet health. Our eyes have been set on the first two areas of innovation: biomolecules and biosystems.
Between these areas, McKinsey forecasts the direct economic impact to be between $1.7 and $3.4 trillion between 2030 and 2040 across (i) human health and performance, (ii) agriculture, aquaculture, and food, (iii) consumer products and service, (iv) materials and energy production, and (v) other.
In our portfolio, S2G has invested in several leading companies involved in the biological revolution, including GreenLight Biosciences, Future Meat Technologies, and NewLeaf Symbiotics. GreenLight Biosciences has been our cornerstone investment into the biomolecule space, specifically RNA-based agriculture and human health solutions.
Why RNA?
Dr. Crick’s groundbreaking research unlocked the potential value of biological innovation. And, the directional flow of information explains why RNA is so important. RNA acts as the architect of life by reading DNA’s blueprint for protein design and carrying out the process of building the protein. While RNA has many functions, mRNA has recently stepped into the limelight with its use in COVID-19 vaccines. At a very high level, mRNA works in these vaccines by sending a message to the architect to build a disease-specific antigen. Other forms of RNA, such as RNAi, work slightly differently by sending a message to halt or inhibit gene expression.
Where are we now?
As the race for a COVID-19 vaccine has continued throughout the year, several leading candidates have emerged using mRNA technology. Pfizer and Moderna have both produced mRNA vaccines with 95.0% and 94.5% efficacy, respectively, in their initial, limited trials. While this is a major milestone for mRNA vaccines, and the broader RNA industry as a whole, there are a series of questions that must be answered including those related to manufacturing, distribution, and a new element uncommonly found in the vaccination process, patient adherence.
Dr. Sandra Fryhofer of the Emory University School of Medicine, representing the American Medical Association, stated in a virtual meeting with the Advisory Committee on Immunization Practices that “we really need to make patients aware that this is not going to be a walk in the park. They are going to know they had a vaccine. They are probably not going to feel wonderful. But they’ve got to come back for that second dose.” Patient adherence to receiving a second dose is essential, because while the vaccine shows early signs of being highly effective, patients will be required to receive a second dose after having potentially unpleasant side effects from the first dose.
Pfizer and Moderna have both worked on solving for manufacturing and distribution complexities in this process. Moderna partnered with Lonza Group AG earlier this year with a 10-year exclusive arrangement to scale the manufacturing process. In early November, Lonza completed its first commercial batch of the main ingredient in the vaccine. Both companies will face complexities with the distribution and supply chain, as both vaccines require very low temperatures for transportation. Despite significant progress on the RNA manufacturing process, the process still remains novel and in many cases can be too expensive compared to existing technologies. While there are many benefits of RNA-based technologies, and the innovation that those technologies may unlock, production cost remains a key concern. Inexpensive RNA production methodologies exist, such as through fermentation, but come at the expense of quality and consistency. Comparatively, chemical synthesis produces high-quality RNA, but generally comes at a prohibitive cost to utilize for many problems.
To democratize RNA-based solutions, the production method requires real, scientific innovation. This innovation in production without sacrificing quality, speed, or flexibility, is precisely what GreenLight Biosciences is bringing to the human and plant health arenas, and the solutions the company is bringing to market have the potential to further unlock the potential of RNA as a real world solution.
RNA Solutions
Beyond vaccines, RNA is a popular topic of research and development for companies, academic institutions, and early-stage business across human health and agriculture. Each area has sophisticated problems that would be better served through RNA-based solutions. In agriculture, RNA-based biopesticides are being developed to reduce off-target impact, eliminate negative soil health implications, and because it is biodegradable, to perform its function without ending up in consumers’ food or water. While no commercialized product has been launched, there has been significant progress made by several organizations across broad acre row crop and permanent crop. In human health, RNA is showing potential to deliver a more effective drug. Although the near-term focus is on vaccines, there is promise on the application of RNA on rare and infectious diseases, specific cancers, and autoimmune disorders.
Conclusion
The world is working on complicated problems, from climate change to chronic human health conditions, and RNA may be a key to unlock new biological technologies that provide a safer, more efficacious solution. S2G remains focused on investing in entrepreneurs on the forefront of biological innovation, who are unlocking new ways to solve complicated problems and to improve human, planet, and climate health.
Catch up with our entrepreneurs on the front line of biological innovation on our podcast Where We Grow From Here with Andrey Zarur, Founder and CEO of GreenLight Biosciences, and Charlie Cooney, a biotech pioneer and Professor of Chemical Engineering at MIT.
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