Two scientists have been awarded the 2023 Nobel prize in physiology or medicine for their contributions to RNA biology that contributed to the unprecedented rate of vaccine development during the Covid pandemic. Prof Katalin Karikó and Prof Drew Weissman share the 11m Swedish kronor (£823,000) prize announced on Monday by the Nobel Assembly at the Karolinska Institute in Stockholm. The Nobel committee awarded the prize for their discoveries concerning “nucleoside base modifications that enabled the development of effective mRNA vaccines against Covid-19”. These vaccines work by smuggling the genetic instructions for making viral proteins into our cells, enabling them to churn out large amounts of this protein and prime the immune cells to fight the virus. A significant obstacle in the development of such vaccines was early prototypes of these synthetic mRNAs provoked inflammatory reactions, making them unsuitable for medical use. Together, Karikó and Weissman discovered that by making small chemical tweaks to the mRNA molecules, they could not only abolish these unwanted inflammatory responses, but also markedly increased production of the target protein. This approach became the basis for the Pfizer and Moderna vaccines. Prof John Tregoning, a vaccine immunologist at Imperial College London, said: “They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it. This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA. “This was a vital building block of the success of the RNA vaccines in reducing disease and death during the pandemic.” Prof Robin Shattock, also at Imperial College London, added that these discoveries “will be key to the successful use of future RNA vaccines and new RNA-based medicines”. Karikó, a research professor at the University of Szeged in Hungary and external consultant to BioNTech in Germany, was said to be “overwhelmed” by the announcement – particularly as she endured decades of scepticism over her work, and was even demoted by the University of Pennsylvania in the mid-90s because of the lack of funding she was generating for her research. She is still an adjunct professor at the university’s Perelman school of medicine. Karikó grew up in a small town in central Hungary, where her family lived in a single room with no running water, no refrigerator and no television. After gaining a postdoc at the Hungarian Academy of Sciences in Szeged, she sold her car, sewed the money into her daughter’s teddy bear and moved her family to Philadelphia, US. She met Weissman, now a professor of vaccine research at the Perelman school of medicine, in the late 1990s over a departmental photocopier at the University of Pennsylvania, where Karikó was printing research papers. The pair struck up a partnership and began investigating mRNA as a potential therapeutic, initially using Weissman’s funding to finance their experiments. Karikó previously told the Guardian she never doubted that their approach would work. “I always wished that I would live long enough to see something that I’ve worked on be approved,” she said. BioNTech and Moderna licensed the modified mRNA technology developed by Karikó and Weissman for their vaccines. Weissman has gone on to develop RNA vaccine candidates against flu, herpes and HIV. Speaking at the announcement of the prize in Stockholm on Monday, the chair of the Nobel committee, Prof Gunilla Carlsson, stressed that their discovery was critical for making the mRNA vaccine platform suitable for clinical use, rapidly, when it was most needed. “I think in terms of saving lives, especially in the early phase of the pandemic, it was very important,” she said. Karikó and Weissman’s work has previously been recognised with the £2.2m Breakthrough prize and numerous other international awards.
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