A Recipe for Hope—Part 1: How mRNA Vaccines Work, opinion

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I was born and raised in Carlsbad and am now in my 5th year of an MD/PhD double doctorate program at the University of Chicago, training to become both a practicing doctor and an experienced scientist, with the research for my PhD in Biochemistry focused on mRNA. As a medical student, I was offered a COVID vaccine when they first became available. I was looking forward to this because of the decades of research behind them and because of the suffering and death COVID had caused among people I knew. So, like more than 96% of US doctors, I chose to get vaccinated1. As the vaccines became more widely available, my friends and family asked me many questions about how they worked.

Firstly, what is mRNA? It is a transient molecule used for translating genes from your DNA, or fixed genetic code, into functional parts like proteins. DNA is stored in the core of your cells, or nucleus, protected from damage by two layers of membrane made of fatty, oily molecules called lipids. You can think of your DNA as a master cookbook of all of your family recipes, stored safely in your pantry. Like your cookbook contains many recipes, your DNA contains many genes, each of which encodes how to make something functional — usually a protein. But like your cells and their proteins, you never need to make all the dishes from your giant cookbook at once. So instead, you might get a piece of paper and copy down the instructions for only the dish you want to make. Similarly, your cells make mRNA as a temporary copy of just one gene and transport it out of the nucleus, where it gets translated into protein. Importantly, DNA lasts for the lifetime of the cell (like a hardcover-bound cookbook stored in the pantry), but RNA and proteins don’t last long (like a paper copy and the dish).

So how do the mRNA vaccines work? They use mRNA to encode the spike protein (from the outside of the COVID virus), which trains your immune system to recognize the virus if it enters your body. The mRNA vaccines are made of only a few components: the mRNA encoding the spike protein, a surrounding lipid membrane, and some stabilizers (sugars, salts, etc.)2. They don’t contain the virus or the parts needed for it to replicate. Like two drops of oil floating in a pot of water, the lipid particle surrounding the vaccine helps it merge with the lipid membrane of your cells. Then your cells produce the spike protein and present it to your immune system. This is similar to taking a printed recipe of something you found online, making the dish using ingredients from your kitchen, and presenting it to your family for them to try. The printed recipe does not go into your pantry or get integrated into your family’s cookbook, like the mRNA from the vaccine doesn’t enter a cell’s nucleus or mess with its DNA. Furthermore, the printed recipe and dish get thrown away when you’re done, just as the mRNA and spike protein degrade. However, your family still tries the dish and would recognize it if they were served it again. In the case of your immune system, it gets trained to recognize the spike protein as something dangerous. Therefore, the effectiveness (and side-effects) of the vaccine are based largely on your immune response.

An understanding of mRNA and how these vaccines are designed combined with a little scientific history makes it easier to grasp how the mRNA COVID vaccines were made so fast. Studies from the early 1990s first showed that injected mRNA could be used to produce a protein using the cell’s machinery and other studies followed to fine-tune this technology3,4. The lipid nanoparticle shell was also the product of more than three decades of research, and was already part of another drug approved by the FDA in 20185. After we learned the genetic code of SARS-CoV2, scientists simply had to choose the right mRNA code and stick it into a ready-made capsule.

Based on data in the clinical trials and my personal observations, the vaccines available against COVID are highly effective and safe, reduce the spread of COVID overall, and provide some hope that we now have a tool to reduce the burden of this treacherous virus6,7.

 

Carlsbad native Caraline Sepich-Poore is a doctoral and medical student at the University of Chicago.

Part 1 of 2: For complete references, please read the article at www.currentargus.com.

By Caraline Sepich-Poore

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