The image at the entrance to the Akademgorodok Technopark immediately explains what makes this neighborhood remarkable. The sign resembling a road sign bears a symbolic drawing "no brain drain". Indeed, the conditions created here are capable of stopping the outflow of scientific personnel. And it's not just the coziness of non-typical low-rise offices and the concentration of laboratory equipment per unit area. World-class projects are implemented here, large-scale tasks that are part of the global agenda are solved. A striking example is the creation by Biosan and Biolabmix of a reagent base for mRNA-based vaccine synthesis. This technology was used to produce the world's first vaccines against SARS-CoV-2 coronavirus.

Biolabmix, established in 2010 on the basis of scientific developments of Biosan, has both an office and a laboratory in the technopark. Both companies were founded by Vladimir Richter, head of the biotechnology laboratory at the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, and specialize in creating solutions for Russian researchers and developers. The main products are nucleoside triphosphates, enzymes, nucleic acid isolation kits, ready PCR reaction mixtures and other reagents for research in molecular biology and diagnostics. The companies, for example, supply reagents to almost all domestic manufacturers of PCR tests.

The accumulated scientific and technological base allowed us to take the next step: to create a platform for synthesizing artificial matrix ribonucleic acid - mRNA. A biological polymer - mRNA - is created from individual components. After the discovery of mRNA in the 60s, scientists around the world have been exploring the possibility of creating new effective drugs for viruses and cancer on its basis. Once in the cells of another organism, mRNA can be expressed and produce the desired protein. That is, having identified a target, it is possible to select which antigen can trigger a specific immune response (in the case of SARS-CoV-2 coronavirus, for example, it was RBD - receptor-binding domain), and deliver it to the cell with the help of a vaccine based on mRNA. Moderna and Pfizer were able to quickly create coronavirus vaccines based specifically on mRNA-based work, giving an explosion of interest in the technology. According to PubMed.gov, while only 188 scientific articles on mRNA vaccines were published worldwide in 2018, in 2022 there will already be 3,277 articles published.

In order to understand what compounds are needed by researchers working in the field of molecular biology, a manufacturer needs a high level of expertise: when you are shaping the market, you need to be well-versed in it yourself. Biolabmix started working on the topic of modified monomers long before interest in mRNA technology became a trend: the first compounds were synthesized in 2016. Today, Biolabmix from Akademgorodok is the only manufacturer in Russia that offers a complete set of reagents for synthesis. Over the past two years, the company has already concluded 180 contracts for the supply of components for mRNA synthesis.

The interview with Vladimir Richter, founder of innovative biotechnology companies Biosan , Biolabmix and Oncostar, Head of the Biotechnology Laboratory at the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, describes how the platform was created, why it became a reality in Novosibirsk Akademgorodok, and what prospects it opens up for the development of domestic pharmaceuticals.

- It follows from the mission of your companies that you create comfortable conditions for researchers and developers. Does this focus on potential customers also distinguish knowledge-intensive business from working in science?

- Yeah. I used to be a researcher myself. And I remember that when you conceived of an experiment, you had to assemble from scratch all the reagent base, instruments, devices to conduct the experiment. Now we give researchers ready-made solutions. Please, choose, use.

- One of your developments is a platform for synthesizing matrix ribonucleic acid. As I understand it, this technology has become very popular in recent years. Can you tell us when you became involved in this topic and what the platform brings to your clients?

- The mRNA synthesis platform has therapeutic applications. With the introduction of Moderna and Pfizer's coronavirus vaccines, there was an explosion of interest in this technology. It was no coincidence that they released vaccines quickly: the approaches were already well-developed, the only thing missing was the object of application. And so it is with us.

We regularly meet with our employees and discuss promising topics. We constantly monitor publication activity, and often communicate with colleagues abroad. Somewhere in 2013-15, we noticed a trend towards mRNA technology.

The reagents of this platform are close to the products we have made in the company before. We also had all the necessary competencies. We just slightly reoriented the direction of research and development in the relevant divisions. And we started to move in this direction, although there was no consumer interest at that time. When it arose, we were able to finalize everything we had quite quickly and offer customers a ready-made solution. Until 2019, we had single orders for the supply of reagents for mRNA synthesis. Everything changed in 2020, when the first coronavirus vaccines triggered an explosion of interest in the technology.

- As far as I understand, it is the platform nature of the solution that is important here. Can you explain what platform means in this case?

- The mRNA molecule consists of many parts. And to assemble this large molecule, one must have, roughly speaking, constructor cubes. These include purely chemical reagents, enzymes, specific equipment (for RNA purification, for quality control), and means of mRNA delivery to the cell. To successfully create a mRNA vaccine with the desired properties, it is necessary to combine all these components in a certain sequence and create a molecule. The platform is all this constructor, which we have made and offer to consumers.

- Who are the consumers right now? Is there already demand for this platform?

- Yes. If we are talking about the world market, the demand is simply enormous. In Russia, it is also constantly growing. Over the last couple of years, we have concluded about 180 contracts for the supply of components for its synthesis. Among our customers are many institutes of the Academy of Sciences, Rospotrebnadzor, medical universities, pharmaceutical companies, competence centers such as Skolkovo or Fiztech, even small private biotech companies. The range of consumers is very wide, and there is a lot of interest.

Virtually all Russian large pharmaceutical companies have recently been strongly interested in creating their own drugs based on mRNA. I have talked to many representatives of the industry, and I can say that there are already about 20 specific targets they are working with.

- What is the global outlook for mRNA technology?

- From my point of view, mRNA is one of the key molecules of the Universe. If we recall the basic dogma of molecular biology, life consists of DNA, where genetic information is stored and transmitted. The realization of this genetic information in the organism takes place through mRNA. Accordingly, if we learn to control it, roughly speaking, at the level of mRNA to block unnecessary function (for example, autoimmune disorders) - this will allow us to switch the functioning of the organism. It is the same if something is missing. There are many inherited diseases that are associated with a deficiency of certain elements. It is possible to deliver to the cell mRNA, which is responsible for the synthesis of these proteins. Accordingly, it is possible to realize the control of the organism through mRNA.

- Am I right in understanding that it is platform solutions, in this case your mRNA synthesis platform, that allow for faster drug development for some new emerging challenge like a pandemic?

- That's exactly what the platform is aimed at. It is enough to identify a target. Knowing it, you can literally create a drug that will be a potential cure within weeks. Let me remind you that an mRNA molecule consists of several parts. The desired function is determined by the middle part of the mRNA molecule, the sequence of ribonucleotides that encode the protein that will be read from this mRNA. All other components are auxiliary. With the use of all these components, the customer can quite quickly create the desired mRNA himself in a laboratory that has the appropriate competence and equipment. So just a week and he has a ready-made molecule.

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. "mRNA is one of the key molecules of the universe - through it the control of the organism can be realized."

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- No one else in Russia has such a platform for mRNA synthesis yet?

- I think so. It is not without reason that the Ministry of Education and Science, according to my information, has been preparing a program for the development of such a platform in Russia for about two years. And this program is divided into parts: someone will be responsible for enzymes, someone for chemistry, someone for delivery. We are familiar with the developers who are planned to be involved in the solution. It is surprising that no one from the ministry is paying attention to the fact that the platform has been around for a long time. We wrote letters to everyone, I went to the heads of the relevant department of the ministry and told them about it. They all said, "Oh, that's great." But they are still developing the program, holding meetings, making reports.

- In general, is there any unified base that would contain biotechnological developments of both scientific institutes and commercial companies, where one could look at the whole range of ready-made solutions in this or that field at once?

- At least I don't know about it. And it's probably impossible to make it. Any commercial structure, if it gets something interesting, immediately classifies the information. For business this is a normal situation, all over the world so. But in science, the only basis is publications in scientific journals.

- But your employees have scientific publications on the platform for mRNA synthesis, right?

- There are separate publications by our employees, and even more so by our partners and customers, where there are references to the fact that they used our company's reagent base.

- In the last few years, the state has allocated quite a lot of money for updating the instrumentation base. Now, due to the need to ensure drug safety, as far as I understand, the program to compensate the costs of scientific basic research is being expanded. Do commercial companies receive any support from the state now?

- I'll start at the end. Commercial companies do not receive support from the state. Moreover, the programs that are implemented through the Ministry of Industry and Trade now do not provide funding for development.

And the fact that the state has invested quite a lot of money is a revelation to me. Every state spends on science as much as it can spend. As an employee of the Institute of Chemical Biology of Fundamental Medicine, I will say that our companies spend many times more on updating the instrumentation base than is allocated to the institute by the state. The company, firstly, has more of its own funds to invest in production development, and secondly, it can concentrate them on the necessary areas. Scientific institutions have a wide range of tasks, and the funds are spread out.

Therefore, I believe that in order to get an effective result, we need to increase funding for science by an order of magnitude. The way they are investing now will not lead to a technological breakthrough anywhere.

- Are scientific institutions in principle capable of switching to a product-based approach? This is a change in thinking.

- You are right, it is a mindset shift, but not only. Publication activity is the main indicator of the achievements of a scientific organization. Now, both ministries and other bodies are gradually shifting to taking into account the specific results of the activities of institutes. But even if rather large grants are allocated for breakthrough technologies, the number of articles, trained young specialists, patents, and conferences is always among the indicators. All this, firstly, distracts from the solution of the target task set for the team, and secondly, leads to the fact that the funds that can be used for a particular research are significantly less than those allocated to you. We have not yet completely gotten away from the problem of assessing performance by article.

- Many developments are made in cooperation with scientific institutes, do I understand correctly?

- Yes. The main part of the products that are now in the catalogs and price lists of our companies were developed either fully or partially at the Novosibirsk Institute of Chemical Biology and Fundamental Medicine. The method of obtaining Biosan 's main product - deoxynucleoside triphosphates, components for PCR - was developed there. For this development, our company together with the institute received a state award of the Novosibirsk region. In fact, the development of our parent company, Biosan, began with this product. We still often cooperate with institutes that have competencies that we do not have. For example, to create components for reagent aftertreatment, we engaged employees of the Institute of Organic Chemistry.

In biotech, most companies, including big pharma, collaborate with research institutes. I know a lot of such examples. From my point of view, this is the right model - to use the competencies of scientific institutes. Of course, on the terms of economic contracts, with financial incentives for employees of the institutes, and so on.

- The path from idea to product emergence in business or in collaboration with a business is faster, perhaps, than in basic science from hypothesis to test sample?

- Of course. If we exclude the extreme situation that we had with the pandemic, in basic science the path to a concrete result is very long. With a company, it's simpler. We need a product that will make money tomorrow. So we have to make it today. This is where the speed of implementation of developments comes from.

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. "For the development of PCR components, our company, together with the institute, received a state award from the Novosibirsk region."

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- In one of your presentations, there is a quote by Daniil Granin about how in Russia you can create anything you want if you can't wait for help.

- It's not "all" there, it's "a lot." This is indeed true. Unfortunately, there are very many regulatory and bureaucratic barriers that stand in the way of development. I have encountered this many times. What I mentioned above - for 2 years now, the ministry has been developing a program to create a mRNA synthesis platform. If we were asking the government for help to develop our own platform, we would still be waiting for help.

We had a similar situation when we faced the problem of increasing production capacity due to the start of COVID-19. The demand for our reagents for PCR tests grew exponentially. In order to meet this demand, we had to expand our production facilities in a short time. We had no working capital, so we appealed to many authorities to help us purchase equipment.

Only at the regional level was there a response, we were granted a loan through a special structure under the regional government. But in the end, we bought everything quickly only thanks to partnership relations with equipment suppliers. They took a risk and supplied it in installments. And they did not fail - we paid off everything quickly.

- I know that researchers are not complacent. Are you working on something else as part of the expansion of the mRNA synthesis platform?

- Yes. The weak link in our platform so far is the lack of our own mRNA delivery system in the cell. We are cooperating with several organizations, I hope for progress in this matter, and I think that by the end of the year we can expect to have our own mRNA delivery system in the cell.

- Are there any other prospects that you and the team are looking at right now?

- There are several of them. For example, genomic editing, which we have been following for a long time, in fact since its emergence. We have reagents and enzymes, but the level of orders and the level of realization is very low. I believe that this technology is still underestimated, and it may well yet catch on. As a scientific direction, it has been firing for a long time. But for me, the shot in the arm is the realization of products. For now, we are just having fun with blanks.

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. "By the end of the year, we can expect to have our own mRNA delivery system in the cell."

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- Am I right in thinking that the research spirit in the team and close communication in the scientific environment allow you not to miss growth points?

- Yes, you're right. Our staff are constantly traveling to conferences, communicating with scientists. Not only in our country, but also abroad. We have many examples where we have come to some actions and solutions thanks to such communication.

- Can you give me an example?

- A very good example is the same platform for mRNA synthesis. The first time we seriously considered that we should make it was when we were talking to representatives of an American company that had implemented this solution by that time. It is clear that in the USA the development of biotech is three orders of magnitude higher than in our country. But we realized that our market would also come there.

- You announced the appearance of a complete platform for mRNA synthesis at the end of last year. Can you estimate the demand for it now?

- Its revenue is growing in proportion to global interest, publication activity, number of clinical trials, and number of patents. In 2022, sales of reagents from this platform are many times higher than in 2021.