How is the COVID-19 mRNA vaccine delivered to cells?

RNA is fragile, and the bloodstream a hostile place for foreign objects. How does the vaccine actually get where it needs to go?

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A woman with long red hair receiving a vaccination shot

Heather Hazzar/SELF Magazine via Flickr

Every vaccine you've ever received has either been a damaged virus, a dead virus, or a protein, a small piece of a virus. The human immune system simply notices the virus or virus fragment and becomes primed to recognize a future infection. 

The recently approved Pfizer and Moderna COVID-19 vaccines are both made of RNA. Instead of delivering a virus or a protein, the RNA codes for cellular instructions for making a SARS-CoV-2 protein which then primes the immune system. But, if the immune system specifically picks up and eliminates foreign particles in the body, how does an RNA vaccine even get to cells without being destroyed?

It's a sticky problem, not least because the human bloodstream is chockfull of RNases, proteins that specifically chew up RNA. These proteins are present in cells, in the blood, and are even excreted by skin cells. Some RNases are called "alarmins," because they are proteins that raise inflammatory response alarms.

There are a few different methods for protecting RNA vaccines from the bloodstream and delivering them into cells (if you're into it you can check them out here). The method used by Pfizer and Moderna uses a "lipid nanoparticle." Their vaccines mix the RNA with lipid molecules. The "lipid," a fat molecule, is positively charged so that negatively charged RNA sticks to it. Given a little time or if you just shake the mixture slightly, the lipid/RNA pairs will assemble into protective particles similar to a soap bubble, with the RNA protected on the inside. The bubbles generally have a neutral charge on the surface, neither positive nor negative, which discourages interest from RNases and the immune system. The immune system is terrific at attacking anything foreign which carries genetic material — like RNA — so the lipid nanoparticle shields the RNA vaccine, quietly shuttling it into the body.

The surface of a cell and the lipid nanoparticle are chemically similar. This allows cells to take up the nanoparticles more easily than naked RNA on its own. Picture it like two soap bubbles inching closer together and then merging. The nanoparticles appear to promote “escape” of RNA into the cell’s cytoplasm, where it’s used by the cell to make the protein that raises an immune response. However, the exact details of this escape are not totally understood. When tested in mice, the vaccine raised immune responses at the highest rates in the lungs, but also in the spleen