There seems to be some confusion about how mRNA coronavirus vaccines work, so let me explain the underlying biology from start to finish. In a normal human cell, DNA in the nucleus is divided into genes. In humans, we have around 25,000 genes.

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These genes contain instructions for making proteins. However, you can’t make proteins directly from the DNA. You need a middleman called messenger RNA, or mRNA. So let’s talk about how mRNA is made.
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During a process called transcription, a sequence of DNA ahead of the gene attracts proteins called transcription factors, which are like blinking lights on an airport landing strip that tells an enzyme called RNA polymerase where to land.
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Once it lands, RNA polymerase unzips the DNA so that the single strands can be read just like how you would open a book to read the pages inside. RNA polymerase then starts reading the DNA and attaches complementary RNA nucleotides to the DNA.
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This forms mRNA, which is then processed by adding a bunch of tags to it like when you check in your bags at the airport. Then the mRNA exits the nucleus through a nuclear pore complex, which for simplicity’s sake you can think of as a hole in the nuclear membrane.
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Once the mRNA leaves the nucleus, it enters the cytoplasm where protein-making machines called ribosomes are located. The mRNA finds a ribosome it likes, and then the fun happens. Remember those tags we talked about?
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If the mRNA has a tag that tells everyone that the final protein needs to exit the cell, the mRNA and ribosome pair find a place to stay on a membranous network of tubules called the endoplasmic reticulum, just like two lovers finding a hotel room.
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In a process called protein translation, the ribosome uses transfer RNA, or tRNA, to bind to a codon (basically a sequence of three mRNA nucleotides) on the mRNA. Each tRNA carries with it an amino acid specific to the codon.
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So for every three mRNA nucleotides, you have a corresponding amino acid carried to it by tRNA to the ribosome. Each amino acid in this growing chain is connected to each other with a peptide bond to eventually form the final protein.
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But we’re not done yet. Once the protein is made, it folds in on itself and then has a bunch of sugars attached to it. These sugars tell the protein where it needs to go.
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If it is to be secreted outside of the cell, the protein goes to the Golgi apparatus, another network of membranous tubules, and is put into a tiny vesicle that then binds to the cell membrane and allows the protein to leave the cell.
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Ok, that was a lot. But now let’s talk about how the coronavirus works and then how companies like Pfizer and Moderna have created mRNA coronavirus vaccines. First, let’s explain what it means for the coronavirus to be a positive-sense single strand RNA virus.
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Essentially, that means it behaves exactly like a malicious piece of self-replicating messenger RNA. When the coronavirus invades a cell, it goes to the host’s ribosomes and forces it to make a bunch of viral proteins including an enzyme called RNA dependent RNA polymerase.
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This enzyme creates a negative-sense coronavirus antigenome that serves as a blueprint to create more positive-sense RNA copies. The virus also hijacks the ribosome to make the infamous coronavirus spike protein and other components it needs to infect other cells.
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What scientists did to create the mRNA coronavirus vaccine is that they only took part of the coronavirus genome that codes for the spike protein and cut away the parts that code for the RNA dependent RNA polymerase and other components of the virus that made it dangerous.
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But then they needed a way for this one piece of spike protein mRNA to invade our cells. If you inject naked mRNA into the blood, it would very quickly be destroyed. RNA has an extra OH group on its sugar backbone compared to DNA that makes it easily destroyed by water.
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So they packaged the mRNA in lipid nanoparticles, which you can think of as tiny soap bubbles made of the same stuff as your cell membranes. These bubbles containing the spike protein mRNA enter the cell membranes of your muscle cells in your arm around the injection site.
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They go to the ribosomes and force them to produce the coronavirus spike protein. Because we have co-evolved with viruses for millions of years, our cells have a way to signal our immune system when they are infected.
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What they do is they break down a random sample of the proteins inside themselves and put them on their cell surface using something called the MHC Class I molecule. Patrolling immune cells, especially T-cells, can recognize these foreign proteins presented on MHC Class I.
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Your immune system learns how to fight these foreign proteins so that the next time you are infected with the real virus there is an army of cytotoxic T cells as well as B cells that produce antibodies to protect you. This is called adaptive immunity and it’s very powerful.
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That, in a nutshell, is how the biology of mRNA coronavirus vaccines work. I hope you all find this useful. Misinformation comes from ignorance, but knowledge is power. Science may seem confusing at first, but at its very core I hope it can be understandable for everyone.
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