2023 Nobel Prize Laureates in Physiology or Medicine: Katalin Karikó and Drew Weissman

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Abstract

The Nobel Prize in Physiology or Medicine in 2023 was awarded to American researchers Katalin Karikó and Drew Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.” The laureates for decades have been searching for strategies to create mRNA-based vaccines and drugs. A method of RNA modification, described by them in 2005, made the creation of mRNA vaccines and mRNA drugs possible. The resulted technology made it possible to use mRNA as a tool for delivering genetic information into cells and into the body. This breakthrough became the basis for the creation of mRNA-based vaccines, which have shown high effectiveness in the fight against infectious diseases and opened the prospect of creating individual anti-cancer mRNA vaccines. The work of Katalin Karikó and Drew Weissman formed the basis of the most widespread vaccines against COVID-19 from Pfizer/BioNTech and Moderna. Although the latest pandemic facilitated creation of a whole set of eff ective vaccines (for example, Sputnik-V), the mRNA vaccines are considered the most innovative and technologically advanced.

About the authors

D. N Antropov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

D. V Prokhorova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

G. A Stepanov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: i@stepanovga.ru
Novosibirsk, Russia

References

  1. Karikó K., Kuo A., Barnathan E. S. Overexpression of urokinase receptor in mammalian cells following administration of the in vitro transcribed encoding mRNA. Gene Therapy. 1999; 6: 1092–1100. doi: 10.1038/sj.gt.3300930.
  2. Fauci A. S., Pantaleo G., Stanley S., Weissman D. Immunopathogenic mechanisms of HIV infection. Annals of Internal Medicine. 1996; 124(7): 654–663. doi: 10.7326/0003-4819-124-7-199604010-00006.
  3. Karikó K., Buckstein M., Ni H., Weissman D. 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. doi: 10.1016/j.immuni.
  4. Limbach P. A., Crain P. F., McCloskey J. A. Summary: the modified nucleosides of RNA. Nucleic Acids Research. 1994; 22(12): 2183–2196. doi: 10.1093/nar/22.12.2183.
  5. Karikó K., Muramatsu H., Welsh F. A. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy. 2008; 16(11): 1833–1840. doi: 10.1038/mt.2008.200.
  6. Morais P., Adachi H., Yu Y. T. The Critical contribution of pseudouridine to mRNA COVID-19 vaccines. Frontiers in Cell and Developmental Biology. 2021; 9: 789427. doi: 10.3389/fcell.2021.789427.
  7. Sahin U., Karikó K., Türeci Ö. mRNA-based therapeutics-developing a new class of drugs. Nature Reviews Drug Discovery. 2014; 13(10): 759–780. doi: 10.1038/nrd4278.
  8. Davis F. F., Allen F. W. Ribonucleic acids from yeast which contain a fifth nucleotide. Journal of Biological Chemistry. 1957; 227(2): 907–915.
  9. Grosjean H. RNA modification: the Golden Period 1995–2015. RNA. 2015; 21(4): 625–626. doi: 10.1261/rna.049866.115.
  10. Frye M., Jaffrey S. R., Pan T. et al. RNA modifications: what have we learned and where are we headed? Nature Reviews Genetics. 2016; 17(6): 365–372. doi: 10.1038/nrg.2016.47.
  11. Boccaletto P., Stefaniak F., Ray A. et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Research. 2022; 50(D1): D231–D235. doi: 10.1093/nar/gkab1083.
  12. Roundtree I. A., Evans M. E., Pan T. et al. Dynamic RNA modifications in gene expression regulation. Cell. 2017;169(7): 1187–1200. doi: 10.1016/j.cell.2017.05.045.
  13. Zhou J., Wan J., Gao X. et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015; 526(7574): 591–594. doi: 10.1038/nature15377.
  14. Chan C. T., Dyavaiah M., DeMott M. S. et al. A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PLOS Genetics. 2010; 6(12): e1001247. doi: 10.1371/journal.pgen.1001247.
  15. Jonkhout N., Tran J., Smith M. A. et al. The RNA modification landscape in human disease. RNA. 2017; 23(12): 1754–1769. doi: 10.1261/rna.063503.117.
  16. Delaunay S., Frye M. RNA modifications regulating cell fate in cancer. Nature Cell Biology. 2019; 21(5): 552–559. doi: 10.1038/s41556-019-0319-0.
  17. Feng Q., Wang D., Xue T. et al. The role of RNA modification in hepatocellular carcinoma. Frontiers in Pharmacology. 2022; 13: 984453. doi: 10.3389/fphar.2022.984453.
  18. Esteve-Puig R., Climent F., Piñeyro D. et al. Epigenetic loss of m1A RNA demethylase ALKBH3 in Hodgkin lymphoma targets collagen, conferring poor clinical outcome. Blood. 2021; 137(7): 994–999. doi: 10.1182/blood.2020005823.
  19. Barbieri I., Kouzarides T. Role of RNA modifications in cancer. Nature Reviews Cancer. 2020; 20(6): 303–322. doi: 10.1038/s41568-020-0253-2.
  20. Cohn W. E., Volkin E. Nucleoside-5′-phosphates from ribonucleic acid. Nature. 1951; 167: 483–484. doi: 10.1038/167483a0.
  21. Penzo M., Guerrieri A. N., Zacchini F. et al. RNA pseudouridylation in physiology and medicine: for better and for worse. Genes (Basel). 2017; 8(11): 301. doi: 10.3390/genes8110301.
  22. Rintala-Dempsey A. C., Kothe U. Eukaryotic stand-alone pseudouridine synthases — RNA modifying enzymes and emerging regulators of gene expression? RNA Biology. 2017; 14(9): 1185–1196. doi: 10.1080/15476286.2016.1276150.
  23. Davis D. R. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Research. 1995; 23(24): 5020–5026. doi: 10.1093/nar/23.24.5020.
  24. Liang X. H., Liu Q., Fournier M. J. Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing. RNA. 2009; 15(9): 1716–1728. doi: 10.1261/rna.1724409.
  25. Nallagatla S. R., Bevilacqua P. C. Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. RNA. 2008; 14(6): 1201–1213. doi: 10.1261/rna.1007408.
  26. Hornung V., Ellegast J., Kim S. et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science. 2006; 314(5801): 994–997. doi: 10.1126/science.1132505.
  27. Andries O., Mc Cafferty S., De Smedt S. C. et al. N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridineincorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. Journal of Controlled Release. 2015; 217: 337–344. doi: 10.1016/j.jconrel.2015.08.051.
  28. Parr C. J. C., Wada S., Kotake K. et al. N1-methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells. Nucleic Acids Research. 2020; 48(6): e35. doi: 10.1093/nar/gkaa070.
  29. Nance K. D., Meier J. L. Modifications in an emergency: the role of N1-methylpseudouridine in COVID-19 vaccines. ACS Central Science. 2021; 7(5): 748–756. doi: 10.1021/acscentsci.1c00197.
  30. Zou S., Toh J. D., Wong K. H. et al. N(6)-methyladenosine: a conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5. Scientific Reports. 2016; 6: 25677. doi: 10.1038/srep25677.
  31. Shi H., Wei J., He C. Where, when, and how: context-dependent functions of RNA methylation writers, readers, and erasers. Molecular Cell. 2019; 74(4): 640–650. doi: 10.1016/j.molcel.2019.04.025.
  32. Yang Y., Hsu P. J., Chen Y. S. et al. Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism. Cell Research. 2018; 28(6): 616–624. doi: 10.1038/s41422-018-0040-8.
  33. Mao Y., Dong L., Liu X. M. et al. m6A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2. Nature Communications. 2019; 10(1): 5332. doi: 10.1038/s41467-019-13317-9.
  34. Chen T., Hao Y. J., Zhang Y. et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 2015; 16(3): 289–301. doi: 10.1016/j.stem.2015.01.016.
  35. Deng L. J., Deng W. Q., Fan S. R. et al. m6A modification: recent advances, anticancer targeted drug discovery and beyond. Molecular Cancer. 2022; 21(1): 52. doi: 10.1186/s12943-022-01510-2.
  36. Richner J. M., Himansu S., Dowd K. A. et al. Modified mRNA vaccines protect against zika virus infection. Cell. 2017; 168(6): 1114–1125.e10. doi: 10.1016/j.cell.2017.02.017.
  37. Chahal J. S., Khan O. F., Cooper C. L. et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. PNAS. 2016; 113(29): E4133–4142. doi: 10.1073/pnas.1600299113.
  38. Wong S. S., Webby R. J. An mRNA vaccine for influenza. Nature Biotechnology. 2012; 30(12): 1202–1204. doi: 10.1038/nbt.2439.
  39. Mehta M., Deeksha, Tewari D. et al. Oligonucleotide therapy: an emerging focus area for drug delivery in chronic inflammatory respiratory diseases. Chemico-Biological Interactions. 2019; 308: 206–215. doi: 10.1016/j.cbi.2019.05.028.
  40. McKenzie L. K., El-Khoury R., Thorpe J. D. et al. Recent progress in non-native nucleic acid modifications. Chemical Society Reviews. 2021; 50(8): 5126–5164. doi: 10.1039/d0cs01430c.
  41. Sharad S. Antisense therapy: an overview. Antisense Therapy. IntechOpen. 2019. doi: 10.5772/INTECHOPEN.86867.
  42. Wan W. B., Seth P. P. The medicinal chemistry of therapeutic oligonucleotides. Journal of Medicinal Chemistry. 2016; 59(21): 9645–9667. doi: 10.1021/acs.jmedchem.6b00551.
  43. Carthew R. W., Sontheimer E. J. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4): 642–655. doi: 10.1016/j.cell.2009.01.035.
  44. Sipa K., Sochacka E., Kazmierczak-Baranska J. et al. Effect of base modifications on structure, thermodynamic stability, and gene silencing activity of short interfering RNA. RNA. 2007; 13(8): 1301–1316. doi: 10.1261/rna.538907.
  45. Mehta A., Michler T., Merkel O.M. siRNA Therapeutics against respiratory viral infections-what have we learned for potential COVID-19 therapies? Advanced Healthcare Materials. 2021; 10(7): e2001650. doi: 10.1002/adhm.202001650.
  46. Chan K. Y., Kinghorn A. B., Hollenstein M. et al. Chemical modifications for a next generation of nucleic acid aptamers. Chembiochem. 2022; 23(15): e202200006. doi: 10.1002/cbic.202200006.
  47. Rohloff J. C., Gelinas A. D., Jarvis T. C. et al. Nucleic acid ligands with protein-like side chains: modified aptamers and their use as diagnostic and therapeutic agents. Molecular Therapy Nucleic Acids. 2014; 3(10): e201. doi: 10.1038/mtna.2014.49.
  48. Sun B. B., Maranville J. C., Peters J. E. et al. Genomic atlas of the human plasma proteome. Nature. 2018; 558(7708): 73–79. doi: 10.1038/s41586-018-0175-2.
  49. Jinek M., Chylinski K., Fonfara I. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012; 337(6096): 816–821. doi: 10.1126/science.1225829.
  50. Yang H., Eremeeva E., Abramov M. et al. CRISPR-Cas9 recognition of enzymatically synthesized base-modified nucleic acids. Nucleic Acids Research. 2023; 51(4): 1501–1511. doi: 10.1093/nar/gkac1147.
  51. Prokhorova D. V., Vokhtantsev I. P., Tolstova P. O. et al. Natural nucleoside modifications in guide RNAs can modulate the activity of the CRISPR-Cas9 System in vitro. CRISPR Journal. 2022; 5(6): 799–812. doi: 10.1089/crispr.2022.0069.
  52. Wienert B., Shin J., Zelin E. et al. In vitro-transcribed guide RNAs trigger an innate immune response via the RIG-I pathway. PLOS Biology. 2018; 16(7): e2005840. doi: 10.1371/journal.pbio.2005840.
  53. Hoy A., Zheng Y. Y., Sheng J. et al. Bio-orthogonal chemistry conjugation strategy facilitates investigation of N-methyladenosine and thiouridine guide RNA modifications on CRISPR activity. CRISPR Journal. 2022; 5(6): 787–798. doi: 10.1089/crispr.2022.0065.

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