Congratulations are in order to Katalin Karikó and Drew Weissman for their Nobel Prize winning work with a COVID-19 vaccine using modified mRNA. The image below shows the component changes that were made to the uridine nucleotide. The change to the middle molecule was that they swapped positions of a carbon and a nitrogen atom in the ring and moved a double bond. In the third molecule they added a methyl (H₃C-) group to one nitrogen of the pyrimidine ring.

In general, if you can change the shape of a molecule, particularly with peptide or nucleotide polymer molecules, you will change the physical properties and the reactivity properties. The Psi nucleotide adds another hydrogen bonding group into the mRNA. These changes add up to lowering the immune response to the vaccine.

The other noteworthy aspect is the very short time it took to get vaccines on the market. This was only possible because decades of research in molecular biology continuously advanced the state of the art. The various funding agencies whose support of basic research over the long haul deserve thanks as well for the timely production of the COVID-19 mRNA vaccine.