Katalin Karikó

Katalin Karikó (Hungarian: Karikó Katalin, Hungarian pronunciation: [ˈkɒrikoː ˌkɒtɒlin]; born 17 January 1955) is a Hungarian biochemist who specializes in RNA-mediated mechanisms. Her research has been the development of in vitro-transcribed mRNA for protein therapies. She co-founded and was CEO of RNARx from 2006–2013.[1] Since 2013 she has been a senior vice president at BioNTech RNA Pharmaceuticals.[2] She is also an adjunct professor at the University of Pennsylvania.[1]

Katalin Karikó
Born (1955-01-17) 17 January 1955
Szolnok, Hungary
EducationUniversity of Szeged
Known formRNA technology in immunology and therapies
ChildrenSusan Francia
Scientific career
Fieldsbiochemistry; RNA technologies
InstitutionsUniversity of Szeged
Temple University
University of Pennsylvania
BioNTech

Karikó's work includes scientific research of RNA-mediated immune activation resulting in the co-discovery with American immunologist Drew Weissman of the nucleoside modifications that suppress the immunogenicity of RNA.[3][4][5] This is seen as permitting the therapeutic use of mRNA.[6] Together with Weissman, she holds U.S. patents for application of non-immunogenic, nucleoside-modified RNA. This technology has been licensed by BioNTech and Moderna to develop COVID-19 vaccines.[7] Karikó married Béla Francia and is the mother of two-time Olympic gold medalist Susan Francia.[6][8]

Early life and education

Karikó grew up in Kisújszállás, Hungary where she attended Móricz Zsigmond Református Gimnázium. After earning her PhD at the University of Szeged, Karikó continued her research and postdoctoral studies at the Institute of Biochemistry, Biological Research Centre of Hungary, the Temple University Department of Biochemistry, and the Uniformed Services University of the Health Science. While serving as postdoctoral fellow at Temple University in Philadelphia, Karikó participated in a clinical trial in which patients with AIDS, hematological diseases, and chronic fatigue were treated with double stranded RNA (dsRNA). At the time, this was considered groundbreaking research as the molecular mechanism of interferon induction by dsRNA was not known, but the antineoplastic effects of interferon were well documented.[9]

Career

In 1990, while a professor at the University of Pennsylvania, Karikó submitted her first grant application in which she proposed to establish mRNA-based gene therapy.[2] Ever since, mRNA-based therapy has been Karikó’s primary research interest. She was on track to become full professor, but grant rejections led to her being demoted by the university in 1995.[7] She stayed on and in 1997 met Drew Weissman, professor of immunology at the University of Pennsylvania.[10]

In a series of articles beginning in 2005, Karikó and Weissman described how specific nucleoside modifications in mRNA led to a reduced immune response.[10][3] They founded a small company and in 2006 and 2013 received patents for the use of several modified nucleosides to reduce the antiviral immune response to mRNA. Soon after, the university sold the intellectual property license to Gary Dahl, the head of a lab supply company that eventually became Cellscript. Weeks later, Flagship Pioneering, the venture capital company who was and still is backing Moderna, contacted her to license the patent. All Karikó said was “we don’t have it.” In early 2013, Karikó heard of Moderna’s $240 million deal with AstraZeneca to develop a VEGF mRNA. Karikó realized she would not get a chance to apply her experience with mRNA at the University of Pennsylvania, so took a role as senior vice president at BioNTech RNA Pharmaceuticals.[2]

Her research and specializations include messenger RNA-based gene therapy, RNA-induced immune reactions, molecular bases of ischemic tolerance, and treatment of brain ischemia.

Scientific contributions

The work and research of Karikó has contributed to BioNTech’s effort to create immune cells that produce vaccine antigens — her research revealed that the antiviral response from mRNA gave their cancer vaccines an extra boost in defense against tumors.[2] In 2020 Karikó's and Weissman's technology was used within a vaccine for COVID-19 that was produced jointly by Pfizer and BioNTech.[6][10] The British ethologist Richard Dawkins as well as the Canadian stem cell biologist Derrick Rossi, who helped found Moderna, have called for these two to receive a Nobel Prize.[11][12][13]

Patents

US8278036B2[14] & US8748089B2[15] — This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.[14][15]

Select publications
  • Anderson BR, Muramatsu H, Nallagatla SR, Bevilacqua PC, Sansing LH, Weissman D, Karikó K (September 2010). "Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation". Nucleic Acids Research. 38 (17): 5884–92. doi:10.1093/nar/gkq347. PMC 2943593. PMID 20457754.
  • Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D (November 2008). "Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability". Molecular Therapy : The Journal of the American Society of Gene Therapy. 16 (11): 1833–40. doi:10.1038/mt.2008.200. PMC 2775451. PMID 18797453.
  • Karikó K, Buckstein M, Ni H, Weissman D (August 2005). "Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA". Immunity. 23 (2): 165–75. doi:10.1016/j.immuni.2005.06.008. PMID 16111635.
  • Karikó K, Weissman D, Welsh FA (November 2004). "Inhibition of toll-like receptor and cytokine signaling--a unifying theme in ischemic tolerance". Journal of Cerebral Blood Flow and Metabolism. 24 (11): 1288–304. doi:10.1097/01.WCB.0000145666.68576.71. PMID 15545925.
  • Karikó K, Ni H, Capodici J, Lamphier M, Weissman D (March 2004). "mRNA is an endogenous ligand for Toll-like receptor 3". The Journal of Biological Chemistry. 279 (13): 12542–50. doi:10.1074/jbc.M310175200. PMID 14729660. S2CID 27215118.

See also

References
  1. "Katalin Karikó". 8th International mRNA Health Conference. Retrieved 2021-01-10.
  2. Keener AB (September 2018). "Just the messenger". Nature Medicine. 24 (9): 1297–1300. doi:10.1038/s41591-018-0183-7. PMID 30139958. S2CID 52074565.
  3. Karikó, Katalin; Buckstein, MIchael; Ni, Houping; Weissman, Drew (2005-08-01). "Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA". Immunity. 23 (2): 165–175. doi:10.1016/j.immuni.2005.06.008. PMID 16111635.
  4. Anderson BR, Muramatsu H, Nallagatla SR, Bevilacqua PC, Sansing LH, Weissman D, Karikó K (September 2010). "Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation". Nucleic Acids Research. 38 (17): 5884–92. doi:10.1093/nar/gkq347. PMC 2943593. PMID 20457754.
  5. Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D (November 2008). "Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability". Molecular Therapy. 16 (11): 1833–40. doi:10.1038/mt.2008.200. PMC 2775451. PMID 18797453.
  6. Kollewe, Julia (21 November 2020). "Covid vaccine technology pioneer: 'I never doubted it would work'". The Guardian. Retrieved 22 November 2020.
  7. Garde, Damian; Saltzman, Jonathan (2020-11-10). "The story of mRNA: From a loose idea to a tool that may help curb Covid". STAT. Retrieved 2021-01-10.
  8. "Katalin Karikó and Drew Weissman. A shared Nobel-prize for mRNA?". Hungarian Free Press. 2020-12-19. Retrieved 2021-01-29.
  9. Schwarz-Romond, Thomas (November 7, 2016). "Transforming RNA research into future treatments: Q&A with 2 biotech leaders". Elsevier Connect. Retrieved 2020-04-27.
  10. Cox, David (2 December 2020). "How mRNA went from a scientific backwater to a pandemic crusher". Wired. Retrieved 26 December 2020.
  11. "Katalin Karikó and Drew Weissman. A shared Nobel-prize for mRNA?". December 19, 2020.
  12. "The hero biochemist who pioneered COVID vaccine tech was professionally spurned for years prior". Salon. 2021-01-25. Retrieved 2021-02-02.
  13. "She was Demoted, Doubted and Rejected But Now Her Work is the Basis of the Covid-19 Vaccine". Good News Network. 2021-02-01. Retrieved 2021-02-02.
  14. US 8278036, Kariko K, Weissman D, "RNA containing modified nucleosides and methods of use thereof", issued 2006-08-21, assigned to University of Pennsylvania
  15. US 8748089, Kariko K, Weissman D, "RNA containing modified nucleosides and methods of use thereof", issued 2013-03-15, assigned to University of Pennsylvania
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