How did a demoted biochemist's trick make mRNA vaccines possible?

Because two obstacles that had stopped mRNA for years were finally removed. An mRNA vaccine delivers a copy of the instructions for one viral protein into cells, which use it as a blueprint to build that protein. Dendritic cells take up the short-lived mRNA, their ribosomes read it, and the viral antigen they produce teaches the immune system. The body degrades the mRNA within a few days, and the mRNA is translated in the cytoplasm and does not affect the genomic DNA in the nucleus.

The idea was not new. In 1990 unprotected lab-made mRNA injected into the muscle of mice made the encoded protein. But in the 1990s mRNA fell out of favor, and many researchers and companies doubted its potential. One of those who kept going was Katalin Karikó. After repeated grant rejections the University of Pennsylvania demoted her in 1995, and she stayed and continued her research.

The first obstacle was inflammation: synthetic mRNA triggered the immune system's alarms. Karikó and Drew Weissman found that replacing uridine with pseudouridine in the mRNA reduced the immune response. The second obstacle was delivery. mRNA is too large to enter cells by simple diffusion, is repelled by the cell membrane, and is quickly destroyed in skin and blood, and wrapping it in lipid nanoparticles solved key barriers.

In December 2020 the UK regulator was the first in the world to approve an mRNA vaccine, and the 2023 Nobel Prize in Physiology or Medicine went to Karikó and Weissman.