WTF Fun Fact 13574 – Katalin Karikó

Katalin Karikó’s journey to Nobel glory is one of resilience and steadfast dedication. A biochemist, Karikó had always been keen on exploring the therapeutic potentials of mRNA.

She obtained her PhD from Hungary’s esteemed Szeged University in 1982 and secured a tenure-track professor position at the University of Pennsylvania in 1989. But her research into RNA faced numerous challenges.

Funding eluded her, and her experiments saw little success. The 1990s brought more trials. This included a cancer diagnosis, the choice to abandon her research or accept a demotion, and a pay cut. She chose the latter, demonstrating her unyielding commitment to mRNA’s potential.

Katalin Karikó”s Partnership with Weissman

1997 marked a turning point. Immunologist Drew Weissman joined the University of Pennsylvania and partnered with Karikó. His interest lay in developing an HIV vaccine. The goal was to prime immune responses with dendritic cells, known for training T cells against foreign antigens. Their collaboration led to the discovery that synthetic, unmodified mRNA provoked dendritic cells into activating inflammatory responses.

The duo’s realization that mammalian cell RNA was frequently chemically modified (while bacterial DNA and RNA often weren’t) changed the course of their research. Another significant insight was that toll-like receptors (TLRs) specifically detected DNA and RNA modifications to trigger inflammation. Their 2005 research paper unveiled that synthetic RNA activated several TLRs, causing inflammatory responses. But adding specific modifications to the synthetic mRNA’s bases curtailed these responses and even enhanced protein production.

mRNA Shaping Modern Vaccine Production

This groundbreaking work ushered in the era of mRNA therapeutics. It catalyzed the inception of Moderna and BioNTech, the companies that later formulated the lifesaving mRNA COVID-19 vaccines. A testament to Karikó and Weissman’s work is the modified base m1 Ψ, now integral to Moderna and Pfizer-BioNTech’s vaccine production.

Recognition Overlooked Despite the promise and subsequent success of her research, Karikó’s contributions remained largely overshadowed. The scientific community’s initial apathy was evident: post their 2005 revelation, Karikó revealed a lack of interest from peers and major biopharma companies. By 2013, this disregard culminated in her departure from the University of Pennsylvania. Yet, adversity wasn’t new to her. Rather than be deterred, she associated with BioNTech, ascending from hands-on benchwork to senior vice presidency. In 2021, she returned to academia, serving at Szeged University and as adjunct faculty at UPenn. Meanwhile, Weissman continued at UPenn, helming the Penn Institute for RNA Innovations.

Katalin Karikó and Nobel Acclaim

The Nobel Prize in Physiology or Medicine awarded to Karikó and Weissman celebrates their persistent, pioneering work on mRNA technology. This research directly paved the way for the creation of the frontrunner COVID-19 vaccines. It’s a fitting tribute to Karikó, who faced professional setbacks and health challenges, yet never deviated from her belief in mRNA’s potential. For her, the Nobel isn’t just an award—it’s validation of decades of unwavering commitment.

The story of Katalin Karikó story serves as an inspiring lesson on perseverance. Her Nobel win, alongside Drew Weissman, underscores the importance of dedication to scientific exploration, even in the face of skepticism and adversity. Their work expanded our understanding of mRNA and provided the foundation for life-saving vaccines during a global pandemic.

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Source: “After being demoted and forced to retire, mRNA researcher wins Nobel” — Ars Technica

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