After being demoted and forced to retire, mRNA researcher wins Nobel
After being demoted and forced to retire, mRNA researcher wins Nobel

          
          
In 1997, Weissman joined UPenn and, with his funding, the two began collaborating on mRNA research. Weissman, an immunologist, was interested in developing a vaccine against HIV and had been focusing on priming immune responses with dendritic cells—an immune cell with the main function of presenting bits of foreign substances (antigens) to T cells to train immune responses against those antigens.
Together, the two realized that synthetic (un-modified) mRNA triggered the dendritic cells to activate inflammatory responses. The finding led them down the path of realizing that RNA in mammalian cells was frequently chemically modified, while DNA and RNA from bacteria and viruses were frequently unmodified. Around the same time, other researchers found evidence that some key proteins that regulate inflammation—toll-like receptors (TLRs)—specifically detect modifications on DNA and RNA to trigger inflammation responses. TLRs are known for recognizing molecular patterns that uniquely identify pathogens.
In their breakthrough 2005 paper, Karikó and Weissman showed that synthetic RNA activates several TLRs, leading to inflammation responses. And, crucially, adding modifications to the bases in the synthetic mRNA—specifically, pseudouridine (Ψ), 5-methylcytidine (m5C), N6-methyladenosine (m6A), 5-methyluridine (m5U) or 2-thiouridine (s2U)—suppressed the inflammation responses. They subsequently showed the modifications could also improve protein production.
Kicked off and kicked out
The finding kicked off the field of mRNA therapeutics and spurred the formation of both Moderna and BioNTech, the two companies that would go on to develop lifesaving mRNA vaccines against COVID-19. Today, m1 Ψ is the most common modified base used in mRNA vaccine production and is present in Moderna and Pfizer-BioNTech's vaccines.
However, the finding received little fanfare among much of the scientific community at the time, and Karikó's research and contribution continued to go largely unappreciated before the pandemic. In 2013, Karikó said she was forced to leave UPenn.
"Ten years ago, I was here in October, because I was kicked out from Penn, was forced to retire," she said in an early morning interview Monday with the Nobel Assembly. She went on to work with BioNTech, doing hands-on benchwork. She became vice president and later senior vice president there. Since 2021, she went back to being a professor, working at Szeged University and as adjunct faculty at UPenn.
Weissman is also still at UPenn, as the Roberts Family professor in vaccine research and director of the Penn Institute for RNA Innovations.


          
                  