The SARS-CoV-2 mRNA vaccines were a success that relied on years of basic scientific research in three general areas: (1) mRNA therapeutics (2) lipid nanoparticle engineering (3) virus research.

The design of therapeutic mRNA was led by Drs. Katalin Karikó and Drew Weismann. Dr. Karikó began her work on mRNA in the 1990’s on building these recipes through biochemistry, with the hitch that our immune system wanted to reject the therapeutic mRNA itself. With Weismann in the mid-2000’s the team showed that a modification in the mRNA made it so that the mRNA would not trigger a non-productive immune response and allow the mRNA to be translated into protein. That is if it could get into a cell to be translated into protein.

This is where the lipid nanoparticles come in. The earliest work on engineering these tiny cargo-ships was published between 1989 and 1991, with research on delivery of mRNA dating back to the 1970s. The field of drug delivery and biomedical engineering, pioneered by Dr. Robert Langer, co-founder of Moderna, works to make medical therapeutics by engineering biology. Many things in our daily life are courtesy of bioengineering -- even if it doesn’t seem so. Take beer for instance, brewers engineered the use of yeast in controlled fermentation to produce alcoholic beverages from the sugars found in plants. Lipid nanoparticles in some form actually exist in our body -- but we call them exosomes -- little signaling carriers that the cells in our body use to talk to each other. Engineers have figured out how to assemble lipid nanoparticles in the lab, and combine them with mRNA to help get the message into our cells. But what is the message?

The message in the context of COVID vaccines is the spike protein which is found on the outside of the virus. The mRNA encodes the spike protein from the SARS-CoV-2 virus with a couple of edits to make sure our immune system can recognize it and launch a strong immune response against the virus. This was led by Dr. Barney Graham (an infectious disease and vaccine researcher), with Drs. Kizzmekia Corbett (a virologist) and Jason McLellan (a protein engineer). Earlier work by Dr. Nianshuang Wang with McLellan on MERS (Middle East Respiratory Syndrome) and SARS (the virus that caused the 2003 epidemic in East Asia) which are also coronaviruses, devised a method to stabilize this spike protein and make it more readily recognized on its own by our immune system.

Now that the 3 pieces existed -- the mRNA, which encoded the stable protein, inside the lipid nanoparticle -- it could rapidly be applied to this novel coronavirus. In reality, these vaccines were the product of 30 years of scientific research that enabled a platform that could easily be adapted to combat the COVID19 pandemic.

To learn more about this subject, watch the following TED-Ed lessons and TED talk:
How does the immune system work?
The surprising reason you feel awful when you're sick
A new superweapon in the fight against cancer

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