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Discoveries and developments making mRNA powerful enough to serve as medicine

The picture above is showing the cover of the peer-reviewed journal Blood in which the BioNTech co-founders’ first mRNA-related publication entitled “Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells” was published in 2006. Since the late 1990, they began a systematic discovery and optimization process to solve the basic problems of RNA: low and short-lived protein production. The 2006 publication was followed by a series of articles in the years 2007 to 2010 describing additional improvements of the mRNA backbone. The systematic principles for mRNA vaccine design introduced by Sahin and Türeci became the widely used standard for optimizing vector scaffolds for mRNA therapy. Discoveries and developments making mRNA powerful enough to serve as medicine.

mRNA technology

  • Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, Yu R, Chandra AK, Waters T, Ruan J, Amisaki M, Zebboudj A, Odgerel Z, Payne G, Derhovanessian E, Müller F, Rhee I, Yadav M, Dobrin A, Sadelain M, Łuksza M, Cohen N, Tang L, Basturk O, Gönen M, Katz S, Do RK, Epstein AS, Momtaz P, Park W, Sugarman R, Varghese AM, Won E, Desai A, Wei AC, D'Angelica MI, Kingham TP, Mellman I, Merghoub T, Wolchok JD, Sahin U, Türeci Ö, Greenbaum BD, Jarnagin WR, Drebin J, O'Reilly EM, Balachandran VP.
    Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. 
    Nature, 2023
  • Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, Maurus D, Schwarck-Kokarakis D, Kuhn AN, Omokoko T, Kranz LM, Diken M, Kreiter S, Haas H, Attig S, Rae R, Cuk K, Kemmer-Brück A, Breitkreuz A, Tolliver C, Caspar J, Quinkhardt J, Hebich L, Stein M, Hohberger A, Vogler I, Liebig I, Renken S, Sikorski J, Leierer M, Müller V, Mitzel-Rink H, Miederer M, Huber C, Grabbe S, Utikal J, Pinter A, Kaufmann R, Hassel JC, Loquai C & Türeci Ö
    An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
    Nature, 2020
  • Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, Bukur V, Tadmor AD, Luxemburger U, Schrörs B, Omokoko T, Vormehr M, Albrecht C, Paruzynski A, Kuhn AN, Buck J, Heesch S, Schreeb KH, Müller F, Ortseifer I, Vogler I, Godehardt E, Attig S, Rae R, Breitkreuz A, Tolliver C, Suchan M, Martic G, Hohberger A, Sorn P, Diekmann J, Ciesla J, Waksmann O, Brück AK, Witt M, Zillgen M, Rothermel A, Kasemann B, Langer D, Bolte S, Diken M, Kreiter S, Nemecek R, Gebhardt C, Grabbe S, Höller C, Utikal J, Huber C, Loquai C, Türeci Ö
    Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
    Nature, 2017
  • Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, Dowd KA, Sutherland LL, Scearce RM, Parks R, Wagner W, Granados A, Greenhouse J, Walker M, Willis E, Yu JS, McGee CE, Sempowski GD, Mui BL, Tam YK, Huang YJ, Vanlandingham D, Holmes VM, Balachandran H, Sahu S, Lifton M, Higgs S, Hensley SE, Madden TD, Hope MJ, Karikó K, Santra S, Graham BS, Lewis MG, Pierson TC, Haynes BF, Weissman D. 
    Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.
    Nature, 2017

  • Frenck RW Jr, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, Perez JL, Walter EB, Senders S, Bailey R, Swanson KA, Ma H, Xu X, Koury K, Kalina WV, Cooper D, Jennings T, Brandon DM, Thomas SJ, Türeci Ö, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. 
    Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents
    New England Journal of Medicine, 2021 
  • Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr, Lena M. Kranz, Kerstin C. Walzer, Stephanie Hein, Alptekin Güler, Jakob Loschko, Mohan S. Maddur, Ayuko Ota-Setlik, Kristin Tompkins, Journey Cole, Bonny G. Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah C. Dany, Stephanie Fesser, Stephanie Erbar, Ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Sänger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie A. Krumm, André P. Heinen, Petra Adams-Quack, Julia Schlereth, Stefan Schille, Christoph Kröner, Ramón de la Caridad Güimil Garcia, Thomas Hiller, Leyla Fischer, Rani S. Sellers, Shambhunath Choudhary, Olga Gonzalez, Fulvia Vascotto, Matthew R. Gutman, Jane A. Fontenot, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil, Andreas A. H. Su, Joshua A. Lees, Nicole L. Nedoma, Ellene H. Mashalidis, Parag V. Sahasrabudhe, Charles Y. Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid L. Scully, Tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion Jr, Kendra J. Alfson, Warren V. Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas N. Kuhn, Özlem Türeci, Philip R. Dormitzer, Kathrin U. Jansen & Ugur Sahin
    BNT162b vaccines protect rhesus macaques from SARS-CoV-2
    Nature, 2021
  • Fernando P. Polack, M.D., Stephen J. Thomas, M.D., Nicholas Kitchin, M.D., Judith Absalon, M.D., Alejandra Gurtman, M.D., Stephen Lockhart, D.M., John L. Perez, M.D., Gonzalo Pérez Marc, M.D., Edson D. Moreira, M.D., Cristiano Zerbini, M.D., Ruth Bailey, B.Sc., Kena A. Swanson, Ph.D., Satrajit Roychoudhury, Ph.D., Kenneth Koury, Ph.D., Ping Li, Ph.D., Warren V. Kalina, Ph.D., David Cooper, Ph.D., Robert W. Frenck, Jr., M.D., Laura L. Hammitt, M.D., Özlem Türeci, M.D., Haylene Nell, M.D., Axel Schaefer, M.D., Serhat Ünal, M.D., Dina B. Tresnan, D.V.M., Ph.D., Susan Mather, M.D., Philip R. Dormitzer, M.D., Ph.D., Uğur Şahin, M.D., Kathrin U. Jansen, Ph.D., and William C. Gruber, M.D., for the C4591001 Clinical Trial Group 
    Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
    New England Journal of Medicine, 2020
  • Edward E. Walsh, M.D., Robert W. Frenck, Jr., M.D., Ann R. Falsey, M.D., Nicholas Kitchin, M.D., Judith Absalon, M.D., Alejandra Gurtman, M.D., Stephen Lockhart, D.M., Kathleen Neuzil, M.D., Mark J. Mulligan, M.D., Ruth Bailey, B.Sc., Kena A. Swanson, Ph.D., Ping Li, Ph.D., Kenneth Koury, Ph.D., Warren Kalina, Ph.D., David Cooper, Ph.D., Camila FontesGarfias, B.Sc., PeiYong Shi, Ph.D., Özlem Türeci, M.D., Kristin R. Tompkins, B.Sc., Kirsten E. Lyke, M.D., Vanessa Raabe, M.D., Philip R. Dormitzer, M.D., Kathrin U. Jansen, Ph.D., Uğur Şahin, M.D., and William C. Gruber, M.D.
    Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates 
    New England Journal of Medicine,  2020
  • Ugur Sahin, Alexander Muik, Evelyna Derhovanessian, Isabel Vogler, Lena M. Kranz, Mathias Vormehr, Alina Baum, Kristen Pascal, Jasmin Quandt, Daniel Maurus, Sebastian Brachtendorf, Verena Lörks, Julian Sikorski, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Grützner, Carsten Boesler, Corinna Rosenbaum, Marie-Cristine, Kühnle, Ulrich Luxemburger, Alexandra Kemmer-Brück, David Langer, Martin Bexon, Stefanie Bolte, Katalin Karikó, Tania Palanche, Boris Fischer, Armin Schultz, Pei-Yong Shi, Camila Fontes-Garfias, John L. Perez, Kena A. Swanson, Jakob Loschko, Ingrid L. Scully, Mark Cutler, Warren Kalina, Christos A. Kyratsous, David Cooper, Philip R. Dormitzer, Kathrin U. Jansen & Özlem Türeci 
    COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses
    Nature, 2020
  • Mark J. Mulligan, Kirsten E. Lyke, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, Kathleen Neuzil, Vanessa Raabe, Ruth Bailey, Kena A. Swanson, Ping Li, Kenneth Koury, Warren Kalina, David Cooper, Camila Fontes-Garfias, Pei-Yong Shi, Özlem Türeci, Kristin R. Tompkins, Edward E. Walsh, Robert Frenck, Ann R. Falsey, Philip R. Dormitzer, William C. Gruber, Uğur Şahin & Kathrin U. Jansen 
    Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults 
    Nature, 2020

 

Engineered Cell Therapies

Protein-based Therapeutics

Small Molecule Immunomodulators

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