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Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo
Open accessAbstract
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5' mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes.
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“These strategies have yielded modest improvements in RNA stability10, 13–16, and thus alternative approaches to RNA stabilization, such as circularization, are desirable.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [14]
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Cites
Dendritic cells and the control of immunity
Banchereau, J., & Steinman, R. M. (1998) · Nature · doi:10.1038/32588 · Cited by 14,486
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Sonenberg, N., & Hinnebusch, A. G. (2009) · Cell · doi:10.1016/j.cell.2009.01.042 · Cited by 3,304
Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625
Self-citationGilboa, E. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31205 · Cited by 589
Quantitating Protein Synthesis, Degradation, and Endogenous Antigen Processing
Princiotta, M. F., Finzi, D., Qian, S.-B., Gibbs, J., Schuchmann, S., Buttgereit, F., Bennink, J. R., & Yewdell, J. W. (2003) · Immunity · doi:10.1016/s1074-7613(03)00051-7 · Cited by 521
Yewdell, J. W., Antón, L. C., & Bennink, J. R. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.1823 · Cited by 450
Weide, B., Pascolo, S., Scheel, B., Derhovanessian, E., Pflugfelder, A., Eigentler, T. K., Pawelec, G., Hoerr, I., Rammensee, H.-G., & Garbe, C. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a00068 · Cited by 378 · cited 1×
“9 In summary, our data reveal 5 0 mRNA cap analogs as a further structural feature to modify the stability and translational efficiency of in vitro transcribed RNA for pharmaceutical applications.”
BackgroundSu, Z., Dannull, J., Yang, B. K., Dahm, P., Coleman, D., Yancey, D., Sichi, S., Niedzwiecki, D., Boczkowski, D., Gilboa, E., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3798 · Cited by 359
(2001) · PubMed Central · Cited by 342
Novel “anti-reverse” cap analogs with superior translational properties
Jemielity, J., Fowler, T. E., Zuberek, J., Stȩpiński, J., Lewdorowicz, M., Niedźwiecka-Kornaś, A., Stolarski, R., Darżynkiewicz, E., & Rhoads, R. E. (2003) · RNA · doi:10.1261/rna.5430403 · Cited by 263
Self-citationResults of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
Weide, B., Carralot, J.-P., Reese, A., Scheel, B., Eigentler, T. K., Hoerr, I., Rammensee, H.-G., Garbe, C., & Pascolo, S. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31815ce501 · Cited by 261
Increased Antigen Presentation Efficiency by Coupling Antigens to MHC Class I Trafficking Signals
Kreiter, S., Selmi, A., Diken, M., Sebastian, M., Osterloh, P., Schild, H., Huber, C., Türeci, Ö., & Şahin, U. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.309 · Cited by 221
Self-citationProbst, J., Weide, B., Scheel, B., Pichler, B. J., Hoerr, I., Rammensee, H.-G., & Pascolo, S. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302964 · Cited by 206
Nair, S. K., Morse, M. A., Boczkowski, D., Cumming, R. I., Vasović, L. V., Gilboa, E., & Lyerly, H. K. (2002) · Annals of Surgery · doi:10.1097/00000658-200204000-00013 · Cited by 205
Current prospects for mRNA gene delivery
Yamamoto, A., Kormann, M., Rosenecker, J., & Rudolph, C. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.09.016 · Cited by 200
Mockey, M., Gonçalves, C., Dupuy, F. P., Lemoine, F. M., Pichon, C., & Midoux, P. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.12.105 · Cited by 165
Phosphorothioate cap analogs stabilize mRNA and increase translational efficiency in mammalian cells
Grudzien‐Nogalska, E., Jemielity, J., Kowalska, J., Darżynkiewicz, E., & Rhoads, R. E. (2007) · RNA · doi:10.1261/rna.701307 · Cited by 152
Self-citationReverse 5' caps in RNAs made in vitro by phage RNA polymerases.
Pasquinelli, A. E., Dahlberg, J. E., & Lund, E. (1995) · PubMed · Cited by 148
Kowalska, J., Lewdorowicz, M., Zuberek, J., Grudzien‐Nogalska, E., Bojarska, E., Stȩpiński, J., Rhoads, R. E., Darżynkiewicz, E., Davis, R. E., & Jemielity, J. (2008) · RNA · doi:10.1261/rna.990208 · Cited by 130
Self-citationVaccination with Messenger RNA (mRNA)
Pascolo, S. (2008) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-72167-3_11 · Cited by 126
Cougot, N., van Dijk, E., Babajko, S., & Séraphin, B. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.06.008 · Cited by 104
Koslowski, M., Şahin, U., Mitnacht‐Kraus, R., Seitz, G., Huber, C., & Türeci, Ö. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1350 · Cited by 97
Self-citationNovel cap analogs for in vitro synthesis of mRNAs with high translational efficiency
Grudzien‐Nogalska, E., Stȩpiński, J., Jankowska‐Anyszka, M., Stolarski, R., Darżynkiewicz, E., & Rhoads, R. E. (2004) · RNA · doi:10.1261/rna.7380904 · Cited by 97
Michiels, A., Tuyaerts, S., Bonehill, A., Corthals, J., Breckpot, K., Heirman, C., Van Meirvenne, S., Dullaers, M., Allard, S., Brasseur, F., et al. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302471 · Cited by 93
Plasmid DNA- and messenger RNA-based anti-cancer vaccination
Weide, B., Garbe, C., Rammensee, H., & Pascolo, S. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.09.012 · Cited by 90
Differential Inhibition of mRNA Degradation Pathways by Novel Cap Analogs
Grudzien, E., Kalek, M., Jemielity, J., Darzynkiewicz, E., & Rhoads, R. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509121200 · Cited by 90
Self-citationImmuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells
Kyte, J. A., & Gaudernack, G. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0161-7 · Cited by 90
Türeci, Ö., Bian, H., Nestle, F. O., Raddrizzani, L., Rosinski, J. A., Tassis, A., Hilton, H., Walstead, M., Sahin, U., & Hammer, J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0724com · Cited by 82
Self-citationSynthetic Messenger RNA as a Tool for Gene Therapy
Rabinovich, P. M., Komarovskaya, M., Ye, Z.-J., Imai, C., Campana, D., Bahceci, E., & Weissman, S. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.1027 · Cited by 73
MS4A12 Is a Colon-Selective Store-Operated Calcium Channel Promoting Malignant Cell Processes
Koslowski, M., Şahin, U., Dhaene, K., Huber, C., & Türeci, Ö. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5768 · Cited by 73
Self-citationTcherepanova, I. Y., Adams, M. D., Feng, X., Hinohara, A., Horvatinovich, J. M., Calderhead, D. M., Healey, D. G., & Nicolette, C. A. (2008) · BMC Molecular Biology · doi:10.1186/1471-2199-9-90 · Cited by 60
Kreiter, S., Konrad, T., Sester, M., Huber, C., Türeci, Ö., & Şahin, U. (2007) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-007-0302-7 · Cited by 51
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Sorted by citations
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
Sahin, U., Derhovanessian, E., Miller, M., Kloke, B.-P., Simon, P., Löwer, M., Bukur, V., Tadmor, A. D., Luxemburger, U., Schrörs, B., et al. (2017) · Nature · doi:10.1038/nature23003 · Cited by 2,488
Self-citationmRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474
Self-citationSystemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
Kranz, L. M., Diken, M., Haas, H., Kreiter, S., Loquai, C., Reuter, K. C., Meng, M., Fritz, D., Vascotto, F., Hefesha, H., et al. (2016) · Nature · doi:10.1038/nature18300 · Cited by 1,819
Self-citationMutant MHC class II epitopes drive therapeutic immune responses to cancer
Kreiter, S., Vormehr, M., van de Roemer, N., Diken, M., Löwer, M., Diekmann, J., Boegel, S., Schrörs, B., Vascotto, F., Castle, J. C., et al. (2015) · Nature · doi:10.1038/nature14426 · Cited by 1,243
Self-citationEngineering circular RNA for potent and stable translation in eukaryotic cells
Wesselhoeft, R. A., Kowalski, P. S., & Anderson, D. G. (2018) · Nature Communications · doi:10.1038/s41467-018-05096-6 · Cited by 853
Metadata
- Authors
- Kuhn, A. N., Diken, M., Kreiter, S., Selmi, A., Kowalska, J., Jemielity, J., Darzynkiewicz, E., Huber, C., Türeci, Ö., & Sahin, U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- University of Warsaw (PL)
- Venue
- Gene Therapy
- Published
- 2010-04-22
- Volume
- 17
- Issue
- 8
- Pages
- 961-971
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2085865810
- Cited by
- 226
- References
- 32
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 19 · 2023: 21 · 2022: 13 · 2021: 20 · 2020: 15 · 2019: 9 · 2018: 16 · 2017: 11 · 2016: 17 · 2015: 12 · 2014: 14 · 2013: 10 · 2012: 7
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (55005604)
- Bundesministerium für Bildung und Forschung
- Ministerstwo Edukacji i Nauki
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mRNA vaccines, RNA stability, translation efficiency, immature dendritic cells, cancer immunotherapy, in vitro transcribed mRNA, immunopharmacology
- MeSH terms
- Dendritic Cells, Half-Life, Humans, Luciferases, RNA, RNA Cap Analogs, Protein Biosynthesis, Vaccines, Synthetic, Genes, Reporter, Antigen Presentation, Cancer Vaccines, RNA Stability, Phosphorothioate Oligonucleotides
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