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In the span of the Covid-19 pandemic, and thanks to the success of two of the currently available vaccines for SARS-CoV-2, messenger RNA, or mRNA, went from being an obscure cell biology concept understood and mentioned only by scientists to being a household term.

But the technology behind the mRNA vaccines from Moderna and Pfizer and BioNTech is anything but new. Developed over an arduous 40 years, it was the result of an unlikely success story. One of the key figures behind this achievement was Katalin Karikó, senior vice president of the German biotech company BioNTech and adjunct associate professor at the University of Pennsylvania.

Speaking at the 2021 STAT Breakthrough Science Summit Wednesday, Karikó shared how despite many, many failures — including demotions, grant rejections, and more — she was clear in her focus. “I always looked to RNA [as a way] to develop therapeutics,” she said, and shared details about her journey to BioNTech as well as her unyielding faith in the technology she was developing.

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Around the world for mRNA

Karikó grew up in Hungary, where at 16 she already knew she wanted to be a scientist, and her dedication to mRNA took her around the world. She wanted to go wherever the best mRNA science was, if that meant academia or biotech, Japan or Pennsylvania, where she worked at Arbutus Biopharma, previously Tekmira. “I was just so determined to go somewhere, do something” with RNA, she said. In 1990, she ended up in Philadelphia, studying the mechanisms of mRNA biology at Penn.

On persevering against the odds

Even though Karikó’s breakthrough research has brought her recognition, and with it grant money, her trajectory was not without its low points. For the first 40 years of her research career, she did not receive a single R01 grant, the main way the National Institutes of Health funds scientists. “There were low points, but every time something went wrong, I tried to focus on the things I could change,” she said. Seeing progress, no matter how gradual, kept her going. “Whether we got more protein, better delivery, or any kind of data, that gave us the push when we were deep in the problems,” she recalled.

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Karikó compared the trajectory of science to rowing, the sport in which her daughter Susan Francia, won Olympic gold medals on the U.S. team in 2008 and 2012. Because rowers face away from the direction in which they’re headed, “They don’t see the finish line, they don’t see how far it is, they just kind of sense it. Science is sometimes like that,” she said.

When biotech calls

Slowly, Karikó started moving into biotech, first by founding her own company, RNARx, in 2006, and then by advancing to bigger companies. Again, she knew exactly where to go: “I was focusing on companies that already had [mRNA] formulations in humans, because then maybe I could help.” She ended up at BioNTech, where she has been since 2013.

Karikó said that biotech has a lot of upsides over academia. “We have to have a product that is functional and will cure people. It was just so much better than a paper, then another paper that maybe nobody will read.”

A shot in the arm

When Covid-19 hit at the beginning of 2020, BioNTech and Karikó switched into overdrive to develop the elements necessary for a vaccine based on their mRNA biology. After months of work, Karikó recounted how, one Sunday night in Philadelphia — her daughter’s birthday, no less — she received a call saying that the vaccine had worked. She wasn’t all that surprised. “I was very happy but [it was] kind of expected,” she said. Seeing not only “the clinical trial data but also how well this modified RNA worked in other infectious disease vaccines was always so powerful.”

Then on Dec. 18, 2020, she got the BioNTech vaccine she had a hand in developing. When she went outside, health care workers who were also getting their vaccines started clapping for her. “They were just so happy. I’m not a very emotional person, but I just cried a little.”

On her newfound fame

When asked her thoughts on possibly being considered for the Nobel prize, Karikó instead focused on the collaborative nature of science and how so many contributions to the mRNA vaccine by others may be overlooked. “Many scientists, just like me, work for years and years and nobody knew about them. And so, I have to represent all of them,” she said.

But she is nostalgic for the days before her newfound fame and workload, she said. “Sometimes I wish I could have that [extra time] back. When I read the title of a very exciting paper, I feel that I would never have time to read that, and I want to because that’s my favorite thing to do.”

The future of mRNA

Karikó sees mRNA, either in the form of vaccines or a therapeutic, as a powerful tool to treat everything from viruses and pathogens to autoimmune diseases, she said. At the beginning of this year, her group published a mouse study showing how an mRNA vaccine could be used to prevent immune system attacks that are common in multiple sclerosis. Although this particular vaccine has a long way to reach the clinic — about two years, she predicted — she believes that her preferred molecule will continue producing new therapies: “I am very hopeful that more and more products will be reaching the market,” Karikó said

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