20 november 2020
21:27
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A tongue twister turns out to be the panacea for filling stadiums again, filling up cafes and grabbing each other without fear. The two most promising vaccines run on a piece of genetic software that will shake up medicine: mRNA.
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The vaccines from the American Moderna and the German / American tandem BioNTech / Pfizer are achieving amazing results in protecting people against coronavirus infection. Both vaccines use the same new revolutionary technology, mRNA, which represents the major breakthrough after 25 years of research. Dissection of a four-letter word that should save us from the Covid pandemic.
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How does it work?
During the explanation it will keep raining acronyms for a while. At the core of all our cells is our DNA, the blueprint with all the genetic code. Think of it as our hardware on which all the information for the production of a total of 3,000 proteins. Each of those proteins represents a function that makes our body run.
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In addition to DNA, there is also RNA. That is a piece of DNA that contains instructions for the production of a protein. Think of RNA as the software, where DNA writes a small piece of our entire genetic code onto a USB stick. That stick is then plugged into our cells, where the task follows – hence the messenger or m (essenger) RNA – protein. Which protein that should be travels along in the RNA code. It consists of a chain of genetic material, the sequence of which determines which protein it will become.
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RNA can be reproduced in a test tube. A copy of the virus RNA, which also has its own genetic QR code, is then dipped in a drop of oil, in the jargon ‘lipid nanoparticles’. That layer around it is necessary because RNA is a very unstable molecule that starts to break down as soon as it comes into contact with substances in blood and cells.
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The vaccine syringe is now ready. After a shot, it enters our cells, the fat layer dissolves and the production of protein starts. Not just any protein, but S protein (contained in the genetic code of the virus). That process makes our cells look like the coronavirus with its typical thorns, like a crown. Because our immune system does not know the foreign crown protein, it starts with the production of antibodies. These are proteins that neutralize the virus so that it cannot reproduce.
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A second buffer is the production of T cells, white blood cells that clear infected cells. Even though both RNA and proteins disappear after a short period of time, in principle our body is sufficiently armed through the build-up of immune memory to fight back with real virus contact. Antibodies and T cells circulate through the blood in our body to critical places such as the nose and lungs. The fact that mRNA dissolves quickly helps explain why a second booster shot is needed after three weeks after a first vaccine shot – the first starts the engine, the second puts a turbo on it.
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Is it hard?
‘The smallest child can make RNA’, says Kris Thielemans. He is an immunologist and professor emeritus and has worked on RNA for 25 years. He has collaborated with Ugur Sahin, the founder of BioNTech. ‘Another question is the lipid nanoparticle, which is new to the pharmaceutical industry. This oil film, a mix of four to five lipids, must be strong enough to keep the RNA outside the body, get it into the cell intact in our body, and at the same time sufficiently soluble to release the RNA so that protein production can begin. ‘ Simply put, it looks like whipping the right mayonnaise. It can also curdle if it is not done properly.
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The oil film around the piece of gene code, a mix of four to five lipids, must be strong enough to keep the RNA outside the body, get it into the cell intact in our body and at the same time sufficiently soluble to release the RNA so that protein production can start.
Kris Thielemans
Emeritus professor en immunoloog (VUB)
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The recipe is a patented trade secret. Thielemans: ‘The fact that Pfizer’s vaccine must be stored at -70 degrees and that of Moderna at -20 is due to a different lipid package. The challenge for the future is to enable storage at room temperature. But that will take a while. If the lipid nanoparticle changes, the vaccine must be fully checked again for safety and effectiveness. ‘
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What are the implications for medical science?
They are big. It doesn’t just open up opportunities for vaccine development. It may also revolutionize cancer therapy as an alternative or complement to surgery, radio and chemotherapy. It works in the same way: injected mRNA activates our immune system and T cells that kill foreign cancer cells.
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A third option is cure for diseases that cause protein deficiency. For example, nebulizing RNA in the lungs could trigger the production of a type of protein – a protein that is now lacking in some people due to a hereditary condition and which leads to cystic fibrosis. It is not so distant anymore that the composition of the lipid nanoparticle determines to which place in our body the mRNA travels – liver or spleen, for example – in order to create a protein explosion locally.
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Are there any catches in the grass?
Because mRNA is such a volatile molecule, it breaks down completely after a short time. So there is no danger that it will change our cell nucleus, our genetic material. Safety is a must, according to Thielemans. A downside is the fat cover that is necessary. Large-scale production by other companies is impossible as long as Pfizer / BioNTech or Moderna do not release their ‘fat recipe’. Criticism of the patents the companies have on it is growing.
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