The key to practical application of mRNA technology: A brief analysis of the 2023 Nobel Prize in Physiology or Medicine

Abstract

The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman in recognition of their contributions to mRNA technology. Before this groundbreaking discovery, mRNA was known to be unstable and can induce inflammatory reactions. Without overcoming this challenge, the progression of mRNA technology towards clinical applications would be hindered. In 2005, Katalin Karikó and Drew Weissman discovered that, unlike naturally synthesized mRNA, in vitro transcribed mRNA led to adverse inflammatory reactions through the release of pro-inflammatory cytokines after being recognized by dendritic cells (DC) as a foreign molecule and subsequent activation of toll-like receptor 3 (TLR3). With this knowledge, they further discovered that, by introducing naturally occurring modified nucleotides to substitute unmodified nucleotides during in vitro transcription, the activation of monocyte-derived dendritic cells (MDDC) induced by mRNA containing these modified nucleotides was significantly reduced and the inflammatory reactions could be nearly eliminated