Early mRNA vaccine breakthrough wins Nobel Prize for medicine, capping off rapid, COVID-fueled rise

Discoveries that enabled mRNA vaccines against COVID-19 have landed two scientists a Nobel Prize. The Nobel Assembly awarded Katalin Karikó, Ph.D., and Drew Weissman, M.D., Ph.D., the prize for their work on nucleoside base modifications, which underpinned the Moderna and Pfizer-BioNTech vaccines that changed the course of the pandemic.  

Working with Michael Buckstein, M.D., Ph.D., and Houping Ni, M.D., Karikó and Weissman began laying the groundwork for mRNA vaccines with a 2005 paper on nucleoside modification. Karikó and Weissman saw that dendritic cells recognize transcribed mRNA as a foreign substance, leading to the activation of the cells and release of signaling molecules. The observation spurred work to learn why the mRNA was recognized as foreign.

Including base modifications in the mRNA almost eliminated the inflammatory response, a discovery that shed light on how cells recognize and respond to the nucleic acids. Two subsequent publications showed modified mRNA increases protein production more than unmodified mRNA. 

Scientists and investors were quick to see the therapeutic promise of the technology. BioNTech set up shop in 2008, followed two years later by Moderna. By 2012, BioNTech was dosing participants with a non-nucleoside modified RNA in a clinical trial. Money flooded into the sector as the leading players attracted VC investment and struck big-ticket deals with a who’s who of Big Pharma companies. 

R&D chugged along at the usual pace through the 2010s, when the early optimism was tempered by setbacks such as the failure of CureVac’s prostate cancer vaccine candidate in a phase 2b. But the rate of progress went supersonic in 2020 as the COVID-19 pandemic provided the ideal proving ground for the idea that mRNA is a faster, more effective vaccine technology than traditional approaches.

Gunilla Karlsson Hedestam, Ph.D., a professor at the Karolinska Institutet and a member of the Royal Swedish Academy of Sciences’ COVID-19 expert group, discussed the impact of Karikó and Weissman’s findings on the pandemic at a press conference to disclose the Nobel Prize winners. 

“What's important here, I think, is that vaccines could be developed so fast. And this was … largely due to improvements in the technology, and this basic discovery that allowed this. So, I think in terms of saving lives, especially in the early phase of the pandemic, it was very important,” Hedestam said. 

The award of the prize illustrates the pace at which mRNA went from a highly promising but unproven technology to a modality used in almost entire populations. At the press conference, Thomas Perlmann, Ph.D., a Karolinska professor, relayed what Karikó said upon hearing the news, explaining how she has undergone “a dramatic change in her circumstances” from losing a job 10 years ago to being a Nobel winner today.