Publications
We maintain a culture of scientific excellence and will continue to drive future innovation through sharing our key findings in a peer reviewed format
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
Cancer
- Hotz C, Wagenaar TR, Gieseke F, Bangari DS, Callahan M, Cao H, Diekmann J, Diken M, Grunwitz C, Hebert A, Hsu K, Bernardo M, Karikó K, Kreiter S, Kuhn AN, Levit M, Malkova N, Masciari S, Pollard J, Qu H, Ryan S, Selmi A, Schlereth J, Singh K, Sun F, Tillmann B, Tolstykh T, Weber W, Wicke L, Witzel S, Yu Q, Zhang YA, Zheng G, Lager J, Nabel GJ, Sahin U, Wiederschain D.
Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models.
Sci Transl Med. 2021 Sep 8;13(610):eabc7804.DOI: 10.1126/scitranslmed.abc7804.
- 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 585, 107–112 (2020). DOI: 10.1038/s41586-020-2537-9
- 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. (2017).
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
Nature. Jul 13; 547(7662):222-226.
- Melief CJM
Cancer: Precision T-cell therapy targets tumours
Nature. 2017 Jul 13;547(7662):165-167. doi: 10.1038/nature23093. Epub 2017 Jul 5. PMID: 28678783.
- Stadler CR, Bähr-Mahmud H, Celik L, Hebich B, Roth AS, Roth RP, Karikó K, Türeci Ö, Sahin U. (2017).
Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.
Nature Medicine Jul; 23(7):815-817. doi: 10.1038/nm.4356. Epub 2017 Jun 12.
- 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. (2017).
Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.
Nature. Mar 9; 543(7644):248-251.
- Grabbe S, Haas H, Diken M, Kranz LM, Langguth P, Sahin U. (2016).
Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma.
Nanomedicine (Lond). Oct; 11(20):2723-2734.
- Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, Grunwitz C, Vormehr M, Hüsemann Y, Selmi A, Kuhn AN, Buck J, Derhovanessian E, Rae R, Attig S, Diekmann J, Jabulowsky RA, Heesch S, Hassel J, Langguth P, Grabbe S, Huber C, Türeci Ö, Sahin U. (2016).
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy.
Nature. Jun 1; 534(7607):396-401.
- Poleganov MA, Eminli S, Beissert T, Herz S, Moon JI, Goldmann J, Beyer A, Heck R, Burkhart I, Barea Roldan D, et al (2015).
Efficient Reprogramming of Human Fibroblasts and Blood-Derived Endothelial Progenitor Cells Using Nonmodified RNA for Reprogramming and Immune Evasion.
Hum Gene Ther. Nov; 26(11):751-766.
- Kreiter S, Vormehr M, van de Roemer N, Diken M, Lower M, Diekmann J, Boegel S, Schrors B, Vascotto F, Castle JC et al (2015).
Mutant MHC class II epitopes drive therapeutic immune responses to cancer.
Nature. Apr 30; 520(7549):692-696.
- Kowalska J, Wypijewska del Nogal A, Darzynkiewicz ZM, Buck J, Nicola C, Kuhn AN, Lukaszewicz M, Zuberek J, Strenkowska M, Ziemniak M, et al (2014).
Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.
Nucleic Acids Res. 42(16):10245-10264.
- Sahin U, Kariko K and Tureci O (2014).
mRNA-based therapeutics–developing a new class of drugs.
Nat Rev Drug Discov. Oct; 13(10):759-780.
- Castle JC, Loewer M, Boegel S, de Graaf J, Bender C, Tadmor AD, Boisguerin V, Bukur T, Sorn P, Paret C et al. (2014).
Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma.
BMC Genomics. 15:190.
- Castle JC, Kreiter S, Diekmann J, Lower M, van de Roemer N, de Graaf J, Selmi A, Diken M, Boegel S, Paret C et al (2012).
Exploiting the mutanome for tumor vaccination.
Cancer Res. Mar 1; 72(5):1081-1091.
- Diken, M., Kreiter, S., Selmi, A., Britten, C. M., Huber, C., Türeci, Ö. & Sahin, U. (2011)
Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation.
Gene Ther. 18, 702–708.
- Kreiter S, Selmi A, Diken M, Koslowski M, Britten CM, Huber C, Tureci O and Sahin U (2010).
Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity.
Cancer Res. Nov 15; 70(22):9031-9040.
- Kuhn, A. N., Diken, M., Kreiter, S., Selmi, A., Kowalska, J., Jemielity, J., Darzynkiewicz, E., Huber, C., Türeci, O. & Sahin, U. (2010).
Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo.
Gene Ther. 17, 961–971
- Kreiter, Sebastian, Selmi, Abderraouf, Diken, Mustafa, Sebastian, Martin, Osterloh, Phillip, Schild, Hansjörg, Huber, Christoph, Türeci, Özlem & Sahin, Ugur. (2008)
Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals.
J. Immunol. 180, 309–318
- Holtkamp, Silke, Kreiter, Sebastian, Selmi, Abderraouf, Simon, Petra, Koslowski, Michael, Huber, Christoph, Türeci, Özlem & Sahin, Ugur. (2006)
Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells.
Blood 108, 4009–4017.
Infectious diseases
- Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, Mizrahi B, Alroy-Preis S, Ash N, Milo R, Huppert A.
Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel
N Engl J Med. 2021 Oct 7;385(15):1393-1400. doi: 10.1056/NEJMoa2114255. Epub 2021 Sep 15. PMID: 34525275; PMCID: PMC8461568.
- 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
N Engl J Med. 2021 Jul 15;385(3):239-250. doi: 10.1056/NEJMoa2107456. Epub 2021 May 27. PMID: 34043894; PMCID: PMC8174030.
- Liu J, Liu Y, Xia H, Zou J, Weaver SC, Swanson KA, Cai H, Cutler M, Cooper D, Muik A, Jansen KU, Sahin U, Xie X, Dormitzer PR, Shi PY
BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants
Nature. 2021 Aug;596(7871):273-275. doi: 10.1038/s41586-021-03693-y. Epub 2021 Jun 10. PMID: 34111888.
- Liu, Y. et al.
Neutralizing Activity of BNT162b2-Elicited Serum
New England Journal of Medicine (2021). DOI: 10.1056/NEJMc2102017
- 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). DOI: 10.1038/s41586-021-03275-y
- Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R. Fontes-Garfias, Hongjie Xia, Kena A. Swanson, Mark Cutler, David Cooper, Vineet D. Menachery, Scott C. Weaver, Philip R. Dormitzer & Pei-Yong Shi
Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
Science. 2021 Mar 12;371(6534):1152-1153. doi: 10.1126/science.abg6105. Epub 2021 Jan 29. PMID: 33514629; PMCID: PMC7971771.
- Muik A, Wallisch AK, Sänger B, Swanson KA, Mühl J, Chen W, Cai H, Maurus D, Sarkar R, Türeci Ö, Dormitzer PR, Şahin U.
Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera
Science. 2021 Mar 12;371(6534):1152-1153. doi: 10.1126/science.abg6105. Epub 2021 Jan 29. PMID: 33514629; PMCID: PMC7971771.
- 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;383:2603-15. DOI: 10.1056/NEJMoa2034577
- 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;383:2439-50 DOI: 10.1056/NEJMMoa2027906
- 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 586, 594–599 (2020). DOI: 10.1038/s41586-020-2814-7
- 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 586, 589-593(2020). DOI: 10.1038/s41586-020-03098-3
Other indications
- Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, Akilli-Öztürk Ö, Kranz LM, Berger H, Petschenka J, Diken M, Kreiter S, Yogev N, Waisman A, Karikó K, Türeci Ö, Sahin U.
A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
Science. 2021 Jan 8;371(6525):145-153. doi: 10.1126/science.aay3638. PMID: 33414215.
Engineered Cell Therapies
- K.Reinhard, B. Rengstl, P. Oehm, K. Michel, A. Billmeier, N. Hayduk, O. Klein, K. Kuna, Y. Ouchan, S.Wöll, E. Christ, D. Weber, M. Suchan, T. Bukur, M. Birtel, V. Jahndel, K. Mroz, K. Hobohm, L. Kranz, M.Diken, K. Kühlcke, Ö. Türeci, U. Sahin
An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors
Science 10.1126/science.aay5967 (2020). DOI: 10.1126/science.aay5967
- Omokoko T, Simon P, Tureci O and Sahin U (2015).
Retrieval of functional TCRs from single antigen-specific T cells: Toward individualized TCR-engineered therapies.
Oncoimmunology. Jul; 4(7):e1005523.
- Simon P, Omokoko TA, Breitkreuz A, Hebich L, Kreiter S, Attig S, Konur A, Britten CM, Paret C, Dhaene K et al (2014).
Functional TCR retrieval from single antigen-specific human T cells reveals multiple novel epitopes.
Cancer Immunol Res. Dec; 2(12):1230-1244.
Antibodies
- Schumacher J, Bacic T, Staritzbichler R, Daneschdar M, Klamp T, Arnold P, Jägle S, Türeci Ö, Markl J and Sahin U (2018).
Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide.
Journal of nanobiotechnology, 16(1), 39. doi:10.1186/s12951-018-0363-0.
- Stadler CR, Bähr-Mahmud H, Celik L, Hebich B, Roth AS, Roth RP, Karikó K, Türeci Ö, Sahin U. (2017).
Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.
Nature Medicine Jul; 23(7):815-817. doi: 10.1038/nm.4356. Epub 2017 Jun 12.
- Christiane R Stadler, Hayat Bähr-Mahmud, Laura M Plum, Kathrin Schmoldt, Anne C Kölsch, Özlem Türeci & Ugur Sahin (2015).
Characterization of the First-in-Class T-Cell Engaging Bispecific Single-Chain Antibody for Targeted Immunotherapy of Solid Tumors Expressing the Oncofetal Protein Claudin 6.
OncoImmunology, 5:3, e1091555, DOI: 10.1080/2162402X.2015.1091555.
- Klamp T, Schumacher J, Huber G, Kuhne C, Meissner U, Selmi A, Hiller T, Kreiter S, Markl J, Tureci O, et al (2011).
Highly specific auto-antibodies against claudin-18 isoform 2 induced by a chimeric HBcAg virus-like particle vaccine kill tumor cells and inhibit the growth of lung metastases.
Cancer Res. Jan 15; 71(2):516-527.
- Sommerhoff CP, Avrutina O, Schmoldt HU, Gabrijelcic-Geiger D, Diederichsen U, Kolmar H (2010).
Engineered cystine knot miniproteins as potent inhibitors of human mast cell tryptase beta.
J Mol Biol. 2010 Jan 8;395(1):167-75. doi: 10.1016/j.jmb.2009.10.028. Epub 2009 Oct 21. PMID: 19852971.
- Avrutina O, Schmoldt HU, Gabrijelcic-Geiger D, Wentzel A, Frauendorf H, Sommerhoff CP, Diederichsen U, Kolmar H. (2008).
Head-to-tail cyclized cystine-knot peptides by a combined recombinant and chemical route of synthesis.
Chembiochem. 2008 Jan 4;9(1):33-7. PMID: 18058774.
- Krause S, Schmoldt HU, Wentzel A, Ballmaier M, Friedrich K, Kolmar H. (2007).
Grafting of thrombopoietin-mimetic peptides into cystine knot miniproteins yields high-affinity thrombopoietin antagonists and agonists.
FEBS J. 2007 Jan;274(1):86-95. Epub 2006 Nov 27. PMID: 17147697.
Small Molecule Immunomodulators
- Vascotto F, Petschenka J, Walzer KC, Vormehr M, Brkic M, Strobl S, Rösemann R, Diken M, Kreiter S, Türeci Ö, Sahin U (2019).
Intravenous delivery of the toll-like receptor 7 agonist SC1 confers tumor control by inducing a CD8+ T cell response.
Oncoimmunology. Apr 19; 8(7):1601480.
