Scientific progress is like a relay race where each new advancement builds on the work of others. Over the years, many discoveries and technologies have made significant strides forward in our journey of understanding. Some of this work is recognized each year with the announcement of the Nobel Prizes in Chemistry, Physics, and Medicine. Though it is impossible to recognize every critical, deserving innovator and idea, the CAS Science Team has identified a number of discoveries with the potential to provide extensive benefits to the scientific community and the broader world. Could one of them be the next Nobel winner?

While much of the world has already seen the impact that mRNA has had on vaccines for COVID-19, it may be time to recognize Dr. Katalin Karikó and Dr. Drew Weissman for their outstanding contributions to nucleoside modifications to suppress RNA immunogenicity on top of their pioneering work on messenger RNA.

Typically, mRNA molecules in their natural state are quickly destroyed when injected into the body, are extremely inflammatory, and cannot instruct cells to make enough viral protein to trigger an immune response. After years of experimentation, Karikó and Weissman created a modified version of mRNA. In this modified version, uridine was substituted with N1-methylpseudouridine (m1Ψ). With this discovery, mRNA transformed into a highly effective vaccine platform. The substitution allows the modified mRNA to avoid immune detection, remain active longer, and enter target cells to create antigens to fight disease.

The mRNA platform is a much quicker platform than the traditional vaccine platforms, which can require protein purification or virus inactivation. The speed of the platform could be vital for treating other diseases and future outbreaks like cancer treatment, immunotherapy, and genetic disease treatment.

CAS has indexed over 500 documents and 50 patents authored by Dr. Karikó and Dr. Weissman, including 7 joint patents. Pfizer/BioNTech and Moderna have licensed their joint patents on nucleoside-modified RNA for COVID-19 vaccines.

Their most cited works include:

Suppression of RNA recognition by toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA, Immunity (2005), 23(2), 165-175. Cited more than 1900 times.

Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability.  Molecular Therapy (2008), 16(11), 1833-1840. Cited over 1400 times.

mRNA Is an Endogenous Ligand for Toll-like Receptor 3, Journal of Biological Chemistry (2004), 279(13), 12542-12550. Cited over 1200 times.

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Photo credits: © Nobel Prize Outreach. Photo: Nanaka Adachi NobelPrize.org. Nobel Prize Outreach AB 2023. Wed. 13 Sep 2023.

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