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Saturday, January 23, 2021

How molecular messenger RNA technology will change the course of various diseases

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(Infographic: Marcelo Regalado)

Every catastrophe has its positive side. Like Ying and Yang. Within all the bad, something good emerges. And that eastern thought could be directly related to the current pandemic that emerged in China by the new SARS-CoV-2 coronavirus that has plagued the world for a year and that It has already caused 93 million infected and almost 2 million deaths.

That little light in the dark is the scientific development behind the new vaccines to prevent the COVID-19 disease, which the new coronavirus generates. And within the batch of vaccines that are already applied in various countries of the world, There are two innovative developments that have shown high efficacy and very good safety, the two basic requirements for its success. They are the genetic vaccines from Pfizer-BioNTech and Moderna laboratories, which use the new messenger RNA platform.

There are two pathogens that cause the most disease out there. They are viruses and bacteria, which even interact with each other and seek to fight each other on the vast battlefield that is nature. RNA, one of the tools that bacteria traditionally use to fight viruses, has become one of the best weapons that humans have discovered to fight the current pandemic caused by a virus.

New genetic techniques in vaccines also transform diseases of the future (Shutterstock)

UC Berkeley biochemist Jennifer Doudna pioneered determining the structure of RNA, helping her and her Ph.D. advisor to discover what the origin of all life on this planet might look like. Then she and her French colleague Emanuelle Charpentier invented an RNA-guided gene editing tool, which earned them the 2020 Nobel Prize in Chemistry. The tool is based on a system that bacteria use to fight viruses. Bacteria develop repeating sequences clustered together in their DNA, known as CRISPR, that can recall dangerous viruses and then deploy RNA-guided scissors to destroy them. In other words, it is an immune system that can adapt to fight each new wave of viruses, just what humans need today.

The year of the plague 2020 will be remembered as the time when these traditional vaccines were supplanted by something fundamentally new: genetic vaccines, that deliver a gene or piece of genetic code to human cells. Genetic instructions then cause cells to produce safe components of the target virus on their own to boost the patient’s immune system and fight it when it enters the body.

For SARS-CoV-2, the virus that causes COVID-19, the key component is its spike protein, which covers the outer envelope and allows it to infiltrate human cells. One method of doing this is by inserting the desired gene, using a technique known as recombinant DNA, into a harmless virus that can carry the gene into human cells. To make a COVID vaccine, a gene is edited that contains instructions to build part of a coronavirus spike protein in the DNA of a weakened virus as an adenovirus, which can cause the common cold. The idea is that the redesigned adenovirus will infiltrate human cells, where the new gene will cause the cells to produce many of these spike proteins.

Genetic vaccines deliver a gene or a piece of genetic code to human cells (Shutterstock)

As a result, the person’s immune system will be prepared to respond quickly if the actual coronavirus strikes. This approach led to one of the earliest COVID vaccine candidates, developed at the Jenner Institute at the University of Oxford. There, the scientists modified the gene for the spike protein into an adenovirus that causes the common cold in chimpanzees, but is relatively harmless in humans.

But another way to introduce genetic material into a human cell and cause it to produce the components of a dangerous virus, such as spike proteins, that can boost the immune system. Instead of transforming the component gene into an adenovirus, you can simply inject the genetic code of the component into humans as DNA or RNA. Regarding the use of the former, until now no easy and reliable delivery mechanism has been developed to introduce DNA vaccines into the nucleus of human cells.

Which leaves us the star molecule in the fight against COVID-19, which is RNA. While DNA remains nestled in the nucleus of our cells, protecting the information it encodes, RNA, on the other hand, comes out and deploys its artillery. The genes encoded by our DNA are transcribed into RNA fragments that exit the nucleus of our cells into the protein-making region. There, this messenger RNA (mRNA) oversees the assembly of the specified protein. In other words, instead of staying at home selecting information, create real products.


The doctors Sydney Brenner from Cambridge and James Watson from Harvard, they first identified and isolated mRNA molecules in 1961. But it was difficult with that technology for the molecule to survive, because the body’s immune system often destroyed the mRNA that researchers designed and tried to introduce into the body. Then, In 2005, a pair of researchers from the University of Pennsylvania, Katalin Kariko and Drew Weissman, demonstrated how to modify a synthetic mRNA molecule so that it could enter human cells without being attacked by the body’s immune system.

When the COVID-19 pandemic struck a year ago, two young and innovative pharmaceutical companies decided to try to take advantage of this role that messenger RNA plays.: the German company BioNTech, which formed a partnership with the American company Pfizer; and Moderna, based in Cambridge, which was supported by Dr. Anthony Fauci and the US government. Their mission was to design messenger RNA that carried the code letters to form part of the coronavirus spike protein and display it in human cells.

BioNTech was founded in 2008 by the husband and wife team of Ugur Sahin and Ozlem Tureci, who met when they were training to be doctors in Germany in the early 1990s. They were both from Turkish immigrant families and shared a passion for medical research, so much so that they spent part of their wedding day working in the lab. They founded BioNTech with the goal of creating therapies that stimulate the immune system to fight cancer cells. It also soon became a leader in the design of drugs that use mRNA in virus vaccines.

Pfizer-BioNTech vaccine against COVID-19 is more than 90% effective - Oliver Bunic / Bloomberg

An mRNA vaccine has certain advantages over a DNA vaccine, which has to use a redesigned virus or other delivery mechanism to penetrate the membrane that protects the nucleus of a cell. RNA does not need to enter the nucleus. It simply has to be delivered to the most accessible outer region of cells, the cytoplasm, which is where proteins are built. The Pfizer-BioNTech and Moderna vaccines do this by encapsulating mRNA in tiny oily capsules, known as lipid nanoparticles.. Moderna had been working for 10 years to improve its nanoparticles. This gave it an advantage over Pfizer-BioNTech: its particles were more stable and did not have to be stored at extremely low temperatures.

In November, Results from the late-stage trials of Pfizer-BioNTech and Moderna returned with compelling findings: both vaccines were more than 90% effective. A few weeks later, with COVID-19 once again emerging across much of the world, they received emergency clearance from the US Food and Drug Administration. And they became the forefront of the biotech effort to roll back the pandemic. The invention of easily reprogrammable RNA vaccines was an ultra-fast triumph of human ingenuityBut it was based on decades of curiosity-driven research on one of the most fundamental aspects of life on planet earth: how genes are transcribed into RNA that tell cells which proteins to assemble.

The COVID-19 pandemic will not be the final plague. However, thanks to new RNA technology, our defenses against most future pests are likely to be immensely faster and more effective. As new viruses emerge, or when the current coronavirus mutates, researchers can quickly recode mRNA from a vaccine to attack new threats. “It was a bad day for viruses,” says Moderna president Noubar Afeyan, a Beirut-born Armenian who emigrated to the United States, about the Sunday he received the results of his company’s clinical trial. “There was a sudden shift in the evolutionary balance between what human technology can do and what viruses can do. We may never have a pandemic again. “


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