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mRNA Vaccine Scientists Win 2023 Nobel Prize

Two winners of the 2023 Nobel Prize in Physiology or Medicine.
Katalin Karikó and Drew Weissman. Credit: Niklas Elmehed © Nobel Prize Outreach.
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The 2023 Nobel Prize in Medicine and Physiology has been awarded to Dr. Katalin Karikó, an adjunct professor of neurosurgery in the University of Pennsylvania (Penn)’s Perelman School of Medicine and Dr. Drew Weissman, the Roberts Family Professor of Vaccine Research in the Perelman School of Medicine.

Karikó and Weissman share the prize for their research on nucleoside base modifications, which began in the 1990s and ultimately enabled the development of life-saving COVID-19 mRNA vaccines.

Early mRNA pioneers

mRNA, short for messenger RNA, is transcribed from DNA and is effectively used as a set of instructions for the creation of proteins by various cellular machinery. Proteins orchestrate and action almost every cellular process, including those required for the development of illness.

For many years, scientists including Karikó and Weissman hypothesized that mRNA could be utilized in vaccine technology or as a therapeutic. The ability to provide cells with the tools required to create a specific protein – such as an antigen – had huge promise.

There were, however, a few issues. In in vitro studies, mRNA was triggering an inflammatory response that majorly hindered its therapeutic potential. The molecule is also highly unstable, requiring a carrier vehicle to effectively deliver it to cells.

Undetermined by the disappointment experienced in their initial experiments working with mRNA, Karikó and Weissman pressed on. Eventually, they created different mRNA variants possessing chemically altered bases. When delivering the variants to a type of immune cell called dendritic cells, the duo found that the dangerous inflammatory response was effectively removed.

The research – published in 2005 – was a significant breakthrough for Karikó and Weissman, who had spent several years studying mRNA by this stage. They had cracked the code and were excited, an emotion that they anticipated would be shared by the scientific community. “I told Kati our phones are going to ring off the hook,” Weissman recalled. “But nothing happened. We didn’t get a single call.”

Clearing the way to clinical applications of mRNA

Once again persistent in their beliefs about mRNA, Karikó and Weissman patented their technology, creating a startup company called RNARx that was dedicated to developing nucleoside-modified mRNA for therapeutic purposes. RNARx eventually shut down due to lack of funding, but Karikó and Weissman continued to study the molecular mechanisms of modified mRNA. In 2008 and 2010, they published research showing that modified mRNA could increase protein production compared to its unmodified form, due to its impact on the enzyme RNA-dependent protein kinase (PKR), which regulates protein production.

In 2010, biotech companies Moderna and BioNTech licensed Karikó and Weissman’s technology, the latter eventually partnering with the pharmaceutical company Pfizer. Each company explored how modified mRNA might be utilized to generate vaccines against several infectious diseases, including Zika and Nipah virus.

In December 2019, reports of the COVID-19 outbreak in China started to emerge and by mid-January, the SARS-CoV-2 viral genome had been published. The biotech companies working with Karikó and Weissman’s technology pivoted their efforts to develop a vaccine against SARS-CoV-2, the first of which entered Phase 1 clinical trials on March 16 2020. In December 2020, the US Food and Drug Administration gave Pfizer–BioNTech’s mRNA COVID-19 vaccines emergency use authorization. It shattered all previous records for the fastest vaccine developed.

“Katalin Karikó and Drew Weissman are brilliant researchers who represent the epitome of scientific inspiration and determination. Day after day, Dr. Weissman, Dr. Karikó and their teams worked tirelessly to unlock the power of mRNA as a therapeutic platform, not knowing the way in which their work could serve to meet a big challenge the world would one day face,” said Penn President Liz Magill. “With the truest devotion to their field, they’ve already promised they will not stop here, and that is the greatest inspiration of all. Our Penn community is enormously proud of their groundbreaking achievements and this well-deserved recognition.”

Surviving the biggest health crises of our time

Collectively, COVID-19 vaccines have saved millions of lives across the globe. After long and difficult periods of enforced lockdown, immunization against the virus slowly offered people the opportunity to resume their lives, to venture back into the world and connect with other people once again. Such joys and safety wouldn’t have been possible had mRNA technology not been ready for its debut. For this, we have decades’ worth of research innovation – including the contributions of Karikó and Weissman – to be grateful for.

“Through their fundamental discoveries of the importance of base modifications in mRNA, this year’s Nobel laureates critically contributed to this transformative development during one of the biggest health crises of our time,” the Nobel Prize committee said.

When initially informed of her win, Karikó thought that somebody was playing a “joke” with her, reassured only by the complex scientific dialogue used in the communication. In an emotive interview, the humble scientist discussed the many difficulties that she has faced in her journey to becoming a Nobel Laureate. Taken from The Nobel Prize.

In the years since the first mRNA vaccines were authorized for human use, this bustling area of biotechnology continues to thrive, with an ever-expanding list of therapeutic applications including novel gene therapies and cancer immunotherapies. Discussing the future of mRNA technology, Weissman said, “It really is exciting. It’s limitless.”