Let There Be Light: GreenLight Strives for Global RNA Equity to Solve Health and Agricultural Problems

Whether it’s pandemics, pesticides, or plant-pests, there are serious health and agricultural threats to humanity. But how do we solve such wide-reaching and complicated problems in a fractured world with countries and regions that are out of alignment and at different technological stages?

GreenLight Biosciences is an integrated life sciences company with an innovative platform to deliver high-quality RNA at a low cost and more quickly than previously possible. By developing RNA products and collaborating with academic and industry leaders, GreenLight Biosciences is on the hunt to advance vaccine development, pandemic preparation, crop management, plant protection, and support the health of bees and other pollinators.

Amongst GreenLight Biosciences growing list of accomplishments is the development and manufacturing of stable double stranded RNA (dsRNA). With this technology, they can target pests or human cells without genetically modifying them through a natural process known as RNA interference (RNAi).

GEN Edge spoke to Martha Ortega-Valle, co-founder and general manager of GreenLight Biosciences’ Human Health division, to discuss how RNA and a global network of manufacturing hubs can help solve the problems of today and the future. (This interview has been lightly edited for clarity.)

GEN Edge: What were the company’s founding mission and vision?

Martha Ortega-Valle: The plan from the beginning, when I started the company with my co-founder Andrey Zarur, was to use technologies that could become solutions that would change the world for the better. We started with sustainability and how RNA can be a part of the agricultural system and the food production system. Why is that important? We use chemical pesticides that have a broad spectrum and are very toxic. They kill many insects and affect ecosystems—that’s not sustainable. So when you move to molecules like RNA in that context, you can get very selective, quite safe, but still efficacious.

Andrey and I had a conversation years ago where we decided that, as we can produce tons of RNA at very low cost, we should expand our capabilities to messenger RNA. Now, everyone understands why mRNA is important. But even then, it was important to therapies and vaccines, where your own body was producing the drug. That’s the elegance of the concept. We were coming from a solution that could manufacture in a very integrated way mRNA for agriculture. We thought those learnings were going to play an important role to accelerate the RNA space. We decided to do it, not only the manufacturing challenge but the pipeline development.

When the COVID-19 pandemic started, we immediately accelerated all the efforts to take that integrated manufacturing platform to GMP. We are seeing that manufacturing and having enough vaccine doses for everyone not only in the developed world—it’s becoming an issue. Even today in Europe, countries are struggling for vaccines and doses. Don’t get me wrong, I think that it’s unbelievable as a society, what we’ve have achieved. But it’s not the time to stop this, it’s the time to push even harder.

At GreenLight, we do believe that [philosophy] to alleviate the inaccess to drugs in general. With vaccines or other therapies that can be based on RNA, we can play an important role. We will not do it alone, but we intend to take that integrated approach to RNA manufacturing so that we can give all geographies independence and the ability to locally own the supply of vaccine doses for the problems at hand and those that we will have to solve in the future.

I don’t think that today there’s a disagreement on whether we should have started building that kind of RNA manufacturing facility three years ago in several regions in the world. Fast forward, we are going to need it. Even if it’s very pressing to vaccinate today, we have to start building in these geographies that don’t have these manufacturing capabilities and we have to be ready for those geographies when boosters are needed or when another pandemic may hit.

Moreover, RNA, which has had its proof-of-concept in vaccines, is a very powerful platform. GreenLight is developing advanced RNA therapies. We have a collaboration with the Gates Foundation on that. Those advanced therapies, in this case, go to Africa. It is our vision that, through this effort of a vaccinated world with a network of facilities, those advanced therapies can also be accessible everywhere. Hopefully, with the innovation put together by all the collective companies in this world that work in RNA, those facilities will have many products to manufacture in 5–10 years. We feel that addressing those very important problems that we’re seeing today in this pandemic is core to our mission, and our technology happens to be right at the core of it.

GEN Edge: Are the agricultural and the biomedical wings of your company independent, or is there a unified way of handling things?

Ortega-Valle: We have a unified way in the sense that we think RNA can solve very important problems in the agricultural space, the human health space, and even animal health. While we have a business that works in agriculture and human health, we have an underlying platform where many learnings can be shared across the different problems that need to be solved in these two different settings.

Thanks to the hyper-integrated manufacturing system that today we have at an industrial scale in Rochester, New York, we were able to have this idea a couple of years ago that we could bring this integration to mRNA. The enzyme systems and the underlying technologies in most cases are being reused. We are manufacturing the same polymerase for agriculture and pharma. In a way, we’re building on top of a technology that has been scaled up to 2,000 liters. With that, you would have more than enough doses. We see that there is strength in using RNA broadly and trying to leverage cross learnings.

When we designed the first product for double-stranded RNA that needed to be stable in the field, we struggled a little because double-stranded RNA is not stable. GreenLight’s team was able to find a formulation that is cost-competitive for agriculture and keeps double-stranded RNA stable for two years at 25℃. That was non-existent three years ago.

We are set in the human health group to create the delivery innovation that is going to make the mRNA vaccines and advanced therapies easy to use from the perspective of handling, storage, etc. We believe we will get there in the same manner that we got there in agriculture.

GEN Edge: It sounds like GreenLight Biosciences is an end-to-end company—from R&D to manufacturing. Why did you take this approach?

Ortega-Valle: To be a master in something you have to do it end-to-end. If you want to know about something, you have to do it yourself. That’s why we are developing end-to-end capabilities. But sometimes the virtue is in the right balance, and sometimes we’re partnering with industry. Ultimately, we’re about solving problems that matter, not about doing every single thing.

We partner extensively with academia, technology companies, and the large pharma companies. Why? Because there is so much space to cover and so many problems to solve, and time is of the essence. We want to get there with RNA not only to solve vaccines but other problems that may be important and treated better with RNA. every disease, but there is a lot of opportunity there because of the elegance of the method and because there’s a lot to control and optimize so that the molecule goes only where it needs to go and do the job efficaciously.

The beauty of that is that you’ll always have one single way of producing that molecule — one platform, a million products. That’s giving you R&D acceleration and then moving them through regulatory and commercial scale. This is the vision, and there is a lot of work that needs to be done by GreenLight and by many collaborators, but it’s very exciting. As a small biotech in Boston, it’s a privilege to be trying to be part of that solution.

GEN Edge: What are your short- and long-term goals?

Ortega-Valle: I want to see those agricultural products replacing chemical products that are used today in the next five years one by one, with the help of cultural companies and governments, and deploy it not only in developed countries but in developing regions. The attraction of the manufacturing makes that a true possibility—one platform, many products. We want to see that change happening. Now we have the technology and manufacturing capability to do it. We need more of those RNA products that can be deployed. We have some, other people will deploy others, but certainly we can manufacture them.

On the human health side, in five years, we need to have this network up and running, even in a shorter time frame. We’re trying to make that a reality. It’s complicated. We’re having conversations with governments and companies to make these complicated endeavors happen.

In ten years, I’d like to have advanced therapies using the RNA platform that can cure or alleviate diseases that don’t have good solutions. We could think about sickle cell disease, HIV, and other important diseases. The intent and community is there, and we’re building the tools. We envision that the network of manufacturing facilities will be there waiting for those products to come to them from many companies that are required to do clinical work and manufacturing in Africa, as well as Europe and the U.S. We are all better when we achieve true global benefit.

GEN Edge: What do you think are the major obstacles for you to get to where you aim to be?

Ortega-Valle: I would not call them obstacles but, rather, important things that need to be addressed. The more ambitious the project, the more things that need to be addressed, right? For the network of global facilities, we are having multiple conversations to be sure that the needed funds are available—but that’s not enough. You need technology companies that cooperate in building those facilities, and those entities need to buy into the project. We are trying to create a consortium of relevant actors that can contribute at each step of the way.

The political alignment is also very important, regionally and globally. We need to make sure to integrate the local people not only in terms of getting their vaccines but also empowers them to have biomanufacturing as part of their industrial endeavors. There are wonderful universities doing great work in those locations that now have access to generate clinical materials in a facility that is local. So, it’s bringing top technologies to those locations.

There are multiple elements that need to be part of the success of this program. We are trying to be deliberate and trying to have the right conversations. There will be important participation by the traditional pharma industry as well. We need them too. They are solving the very important problem of today, which is the manufacturing of vaccines. We are going to ask them to also be part of this initiative of building the manufacturing of RNA for the boosters to come, the pandemics to come. It’s a collective effort.

I’m optimistic about being able to get those elements that are essential aligned. It won’t be easy, but we have all the pieces. We just have to have the motivation, the support, and the intention to put them together.