Congratulations to Katalin Karikó and Drew Weissman who were jointly awarded the 2023 Nobel Prize in Physiology or Medicine for their work which led to the development of effective mRNA vaccines against COVID-19.1
mRNA: a breakthrough in vaccine technology
Messenger RNA (mRNA) is a molecule found in living organisms which allows for the production of proteins. It was postulated as far back as the 1980’s that mRNA has the potential for use as a vaccine platform following early experiments showing that proteins can be artificially produced from mRNA when inserted into various types of cell.2 It was later shown that mRNA coding for proteins from pathogens, such as viruses, could induce an immunogenic response. mRNA vaccines also have many advantages compared to conventional vaccines. For example, as the COVID-19 pandemic has shown, they can be designed, tested, optimised and mass-produced at considerable speed.
One of the problems with early mRNA vaccines was the mRNA molecule itself was recognised by the recipient’s immune system as being foreign and caused an inflammatory response before the intended protein could be produced. Katalin Karikó and Drew Weissman at the University of Pennsylvania discovered in 2005 that replacing uridine with pseudouridine3 (a naturally occurring isomer of uridine) shields the resulting mRNA from the recipient’s immune system. Karikó and Weissman later discovered that the uridine to pseudouridine modification also enhances the stability of mRNA and capacity for it to be translated into protein, further increasing its potential for use as an mRNA vaccine.4.5
Both the Pfizer/BioNTech and Moderna COVID-19 vaccines Comirnaty® and Spikevax®, respectively, and next-generation vaccines contain the pseudouridine modification N1-methylpseudouridine (m1Ψ) which is a focus of the ongoing global patent litigation between the companies at the time of writing. Other important aspects of mRNA vaccine technology include the use of other key modifications of the mRNA and the components of the lipid nanoparticles (LNPs) which are important mRNA delivery vehicles.
The 2023 Nobel Prize in Physiology or Medicine is therefore a key milestone for mRNA vaccine technology and is likely to shape innovation and the development of future vaccines. We expect that patents directed to fundamental aspects of mRNA technology also have the potential to shape the mRNA vaccine landscape. We will be closely monitoring the COVID-19 mRNA vaccine litigation for an insight into what the future holds for patentees and other stakeholders in this exciting new field of medicine.
Our team has considerable experience advising clients on patent matters in relation to mRNA vaccines and other RNA therapeutics including: RNA interference (RNAi), antisense oligonucleotides, non-coding RNA (ASO), CRISPR-based genome editing and LNP chemistry so please get in touch if you have any related queries!
1 https://www.nobelprize.org/prizes/medicine/2023/press-release/
2 Malone, R.W., Felgner, P.L., Verma, I.M. Cationic liposome-mediated RNA transfection. Proc Natl Acad. Sci. USA 86 6077-6081 (1989).
3 Karikó, K., Buckstein, M., Ni, H. and Weissman, D. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
4 Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833-1840 (2008).
5 Anderson, B.R., Muramatsu, H., Nallagatla, S.R., Bevilacqua, P.C., Sansing, L.H., Weissman, D. and Karikó, K. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884-5892 (2010).