Is the mRNA vaccine a bioengineering discovery of the decade?

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2020 is likely to go down in history forever as a year in which all of humanity fought hard against the coronavirus and COVID-19. But while in February and March 2020, according to photos and videos from Italy, it appeared that the coronavirus was winning this war, by the end of 2020 the SARS-CoV-2 vaccine appears to be close. Specifically, these are mRNA vaccines developed by Moderna Therapeutics and a consortium of the startup BioNTech and the pharmaceutical giant Pfizer. Why are these vaccines great? And can they represent the bioengineering triumph of the decade? We will talk about this in today’s batch. Short Note: Any information in this episode is not intended and should not be construed as medical advice.

Let’s say a simple thing, but for some reason often questioned: vaccines save millions of lives around the world every year, and thanks to them we have practically eradicated the true disgust, that is smallpox, we have minimized the incidence of polio and significantly minimized the onset of whooping cough. Typical classic vaccines are usually based on the administration to the body of an attenuated or dead pathogen, a harmful element from which we want to protect ourselves, or even just a part of it. Our immune system remembers this weakened pathogen and ideally does not give it a chance in the future to multiply in us to the point of causing disease.

Because we are interested in new approaches in vaccine development, because even conventional vaccines have their weaknesses and various obstacles prevent us from using them effectively. Some pathogens can very well escape the immune system response. For other viral diseases, the problem is not the effectiveness of conventional vaccines, but the fact that they take a long time to develop and are difficult to distribute quickly and on a large scale. Finally, classical approaches may not be effective against noncommunicable diseases such as cancer. We need to be ambitious and also consider how to protect ourselves from such diseases.

What exactly is this mRNA? MRNA, or “messenger RNA”, is a transition step between the DNA that encodes information for the production of proteins and the proteins themselves. In other words, the basic dogma of biology tells us that information stored in DNA is transcribed into mRNA in the transcription process, and this information is translated into the language of amino acid chains that make up new proteins in the process of translation into structures. cell phones called ribosomes.

Vaccines literally train the immune system to recognize a certain structure of the virus that can cause disease. Unlike typical vaccines, which contain attenuated, or purified viruses, that is, “purified” components of a virus, an mRNA vaccine directly provides a person with genetic material, an mRNA that has encoded genetic information to produce a protein that is part of a virus, in our unfortunate case SARS-CoV-2. When they inject this vaccine into our body, such as the shoulder muscle, our cells, based on the model of this mRNA, start producing a protein that is part of the coronavirus, just as a virus would make new proteins through its RNA. Well, don’t worry – such a viral protein won’t cause us COVID-19. However, the presence of a viral protein is enough for our immune system to be able to imagine what a real virus looks like. This gives the immune system the ability to produce antibodies that can kill the real virus if a person becomes infected.

Imagine a virus like a terrorist with a machine gun who wants to go through an airport check-in plane and have a sharapata there. Genetic information in the mRNA form of a certain viral protein is harmless, just like an unloaded submachine gun, trigger, and magazine. This is only good for killing nails and not for causing international accidents. However, if the immune system, that is, the airport security service that checks the backpacks, has already seen the images of the machine gun without a trigger or ammunition, in the future it will safely recognize the real machine gun and send the malicious terrorist not on the plane but into the dungeon. .

Ultimately, therefore, a well-optimized mRNA vaccine should be very safe, not least because it cannot reproduce in the body. And why do I say well optimized? This is more of a topic for connoisseurs, but with the mRNA vaccine we can play with various parameters: the so-called polyadenine tail allows to increase its stability and increases the amount of protein translation, as well as the optimization of the codon. Purification of the mRNA in turn reduces the activation of the immune system. And this is where synthetic biology comes into play to a large extent. It is precisely the methods of designing a new synthetic ANN, understanding the various effects of its structures on the function and guaranteeing its reliable production that allow us to make things meaningful of mRNA. Also, for gourmets, I will mention that we have different types of mRNA vaccines: we divide them, for example, based on their ability to replicate in vivo.

But let’s move on. The big disadvantage of traditional vaccine development is their slow development, as I said earlier. And for example, yesterday, a week ago or a month ago we wanted the SARS-CoV-2 vaccine! On the contrary, let’s take the classic case of the development of the flu vaccine. It usually takes about 6 months to identify a viral strain circulating around the world. This candidate virus is then grown in the laboratory for several weeks to become a less dangerous hybrid virus capable of growing in chicken embryos. This hybrid virus is then introduced into the eggs of fertilized hens and incubated for several days to make more copies. Then the fluid is collected from the infected eggs, the viruses are killed and their proteins are purified for several days and … Do you find this process long and complicated?

Again, mRNA vaccines can show their strength. In addition to the fact that the mRNA molecule itself is not dangerous and cannot cause disease, it is relatively easy in modern manufacturing procedures and sterile precautions to produce it to a level of purity corresponding to a medical standard. Furthermore, nucleic acids are much better designed than proteins, which have much more complicated secondary and tertiary structures. Today, synthetic biology has reached the point where we can design small pieces of RNA to bind to other RNA molecules with a precisely defined force and then regulate them – my mathematical analysis and computer simulations of one of these regulatory genetic systems. they upset my research.

How fast was the mRNA vaccine project for COVID-19? Very fast. But such that party. A few days after scientists were able to scan (or, professionally, sequence) the genetic code of the SARS-CoV-2 coronavirus, we already had bits of mRNA that were candidates for the correct coronavirus vaccines. Of course, these vaccines have had to go through clinical trials, from lab tests to human tests – and this week, mRNA vaccines have proven effective in Phase 3 clinical trials. For Moderna Therapeutics’ mRNA-1273 vaccine, this study was conducted on 30,000 participants. Of these, 95 received COVID-19, while only 5 diseases occurred among vaccinated people, while 90 people were infected in the placebo group. According to the calculations, this corresponds to an efficiency of 94.5%. What about the severity of the symptoms? None of the vaccinated had a severe course of COVID-19, while 12% of the unvaccinated infected had a severe course.

What is another benefit of mRNA vaccines? It appears that they could be used for a wider range of diseases, such as some cancers. In addition to research on RNA vaccines in the fight against infectious diseases such as influenza viruses, Ebola or Zika, there are currently about 50 clinical trials with RNA vaccines against tumors such as leukemia, melanoma or the dreaded glioblastoma, brain tumors.

So when did researchers start thinking about mRNA vaccines? For the first time, animals successfully demonstrated that mRNA could be used to elicit an immune response in 1990. Then, however, research on mRNA and its use in vaccination somehow stopped and the scientists they started working on another nucleic acid that we all know: DNA. Because? They simply feared that mRNA was unstable, had high intrinsic immunogenicity, that is, the ability to elicit a strong immune response in the body, and at the same time it was very difficult to reasonably deliver it to the human body. Just an unpromising way, right?

But a lot has changed in the last decade. Many new technologies have seen the light of day: from fast sequencing, to cheaper and more accurate nucleic acid synthesis, to high-quality software tools with which we can better model, design and then predict the effect of mRNA structures. We can also deliver mRNA better to cells – we use fat globules called liposomes – you may recall my conversation with Professor Kate Adamala, who uses similar liposomes to build synthetic cells.

And, of course, we must not forget automation: aunts and uncles in white coats with carpal tunnels caused by endless pipetting are still disappearing from biological laboratories and will be replaced by laboratory robots. The combination of these factors not only increases the chances of developing effective mRNA vaccines, but also reduces the logistical difficulties and financial costs associated with their production, making mRNA vaccines potentially much more affordable. However, the logistics are not easy. MRNA is inherently unstable, and Pfizer and BioNTech vaccines, for example, will likely need to be stored at -80 degrees Celsius – a temperature your poor freezer at home doesn’t just evoke. Therefore, the logistical challenges associated with mRNA vaccination remain.

The advent of mRNA vaccines is truly an admirable triumph of bioengineering and biotechnology and synthetic biology. Furthermore, it appears that this technology will be available in record time. So is the mRNA vaccine a bioengineering discovery of the decade? I don’t know, because I think we have even more peels in the field of synthetic biology in this decade. But the mRNA vaccine will certainly be among the best candidates for the ultimate innovation of this decade.

References:

[1] Weiss, R., Scheiblhofer, S. and Thalhamer, J. (2017). Generation and evaluation of prophylactic mRNA vaccines against allergy. In Molecular Biology Methods. https://doi.org/10.1007/978-1-4939-6481-9_7

[2] Pardi, N., Hogan, MJ, Porter, FW and Weissman, D. (2018). mRNA vaccines: a new era in vaccinology. Nature Reviews Drug Discovery. https://doi.org/10.1038/nrd.2017.243

[3] Chen, N., Xia, P., Li, S., Zhang, T., Wang, TT, & Zhu, J. (2017, May 1). RNA sensors of the innate immune system and their detection of pathogens. IUBMB Life. Blackwell Publishing Ltd. https://doi.org/10.1002/iub.1625

[4] How Pfizer and Moderna mRNA vaccines work, why they are a breakthrough and why they need to be kept so cold. (nd). Retrieved November 20, 2020, from https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be – kept-so-cold-150238

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