Nobel Prize for work that led to mRNA vaccines

The 2023 Nobel Prize in Physiology or Medicine has been awarded jointly to Professor Katalin Karikó and Professor Drew Weissman for their discoveries relating to nucleoside base modifications, which contributed to the development of mRNA vaccines.

Their research was vital in the development of effective vaccines, at an unprecedented rate, during the COVID-19 pandemic. Both the Moderna and Pfizer/BioNTech vaccines were based on the mRNA platform that Professor Karikó and Professor Weissman developed.

Professor Wiseman told the BBC: 'I would go to meetings and present what I was working on, and people would look at me and say: "Well, that's very nice, but why don't you do something worthwhile with your time, mRNA will never work." But Katie and I kept pushing'.

The mRNA vaccine platform works by introducing small pieces of RNA into the body's cells, which use the cell's own machinery to manufacture small pieces of viral protein. In turn, these proteins cause the immune system to produce antibodies against the specific pathogen.

However, early research showed that these synthetic mRNAs triggered inflammatory responses, making them unsuitable for clinical use. As a result, said Professor Weissman, 'pretty much everybody gave up on it'.

Professors Karikó and Weissman discovered that making small modifications to the nucleoside bases in the mRNA molecules not only eliminated the unwanted inflammatory responses, but also significantly increased production of the target protein.

Professor Robin Shattock, an immunologist at Imperial College London (who was not involved in the research), said: 'The seminal work of Katalin Karikó and Drew Weissman... was critical to the success of the highly effective mRNA vaccine against COVID-19. Their fundamental work in using modified nucleotides, the building blocks of RNA, to avoid activation of the innate immune system will be key to the successful use of future RNA vaccines and new RNA-based medicines.'

Professor Karikó, a Hungarian research scientist, was appointed assistant professor at the University of Pennsylvania In 1989. There, she experimented with different forms of RNA, with hoping to optimise the expression of therapeutic proteins.

In the late 1990s, she teamed up with Professor Weissman, an American physician and immunologist who focused on vaccine research. He had joined the University of Pennsylvania in 1997. Professor Karikó's expertise in RNA biochemistry complemented Professor Weissman's background in immunology, with both scientists aiming to advance the mRNA platform for clinical use.

After watching the official announcement of her Nobel laureateship, Professor Karikó said 'I was very much surprised but I am very happy'.

'The future is just so incredible,' Professor Weissman added. 'We've been thinking for years about everything that we could do with RNA, and now it's here.'