The pivotal role of uridine modifications in the development of mRNA technology

Abstract

In 2023, Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their nucleoside base modifications research that later enabled mRNA vaccine development against COVID-19. This paper briefly reviews these achievements in the context of the development of mRNA technology and its enormous potential for medicine in the prevention of various infectious diseases and cancer treatment, including personalized therapies. It is beyond any doubt that discoveries made by Karikó and Weissman were pivotal in overcoming one of the major hurdles in the practical application of mRNA molecules, i.e., their recognition by endosomal Toll-like receptors and downstream innate immune response, ultimately leading to the decreased translational activity of exogenous mRNA molecules and their degradation. Although the Nobel Prize for Karikó and Weissman is fully justified, it must be stressed that the mRNA technology would never unfold its potential for public health without a collective scientific effort encompassing over 40 years of research.