N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density
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Certain chemical modifications confer increased stability and low immunogenicity to in vitro transcribed mRNAs, thereby facilitating expression of therapeutically important proteins. Here, we demonstrate that N1-methyl-pseudouridine (N1mΨ) outperforms several other nucleoside modifications and their combinations in terms of translation capacity. Through extensive analysis of various modified transcripts in cell-free translation systems, we deconvolute the different components of the effect on protein expression independent of mRNA stability mechanisms. We show that in addition to turning off the immune/eIF2α phosphorylation-dependent inhibition of translation, the incorporated N1mΨ nucleotides dramatically alter the dynamics of the translation process by increasing ribosome pausing and density on the mRNA. Our results indicate that the increased ribosome loading of modified mRNAs renders them more permissive for initiation by favoring either ribosome recycling on the same mRNA or de novo ribosome recruitment.
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Nucleoside-modified mRNA can reduce the activation of TLRs, retinoic acid-inducible gene I (RIG-I), protein kinase R (PKR), and 2′-5′-oligoadenylate synthetase (OAS); additionally, nucleoside modification increases translation activity and resistance against RNase L-mediated degradation.
“Nucleoside-modified mRNA can reduce the activation of TLRs, retinoic acid-inducible gene I (RIG-I), protein kinase R (PKR), and 2′-5′-oligoadenylate synthetase (OAS). Additionally, nucleoside modification increases translation activity and resistance against RNase L-mediated degradation.54,81,173–176”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [176]
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Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M., et al. (2012) · Nature · doi:10.1038/nature11112 · Cited by 4,884 · see citing works
Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C. E., & Jaffrey, S. R. (2012) · Cell · doi:10.1016/j.cell.2012.05.003 · Cited by 4,223 · see citing works
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 · see citing works
Self-citationKarikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728 · see citing works
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662 · see citing works
mRNA-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 · see citing works
Ingolia, N. T., Lareau, L. F., & Weissman, J. S. (2011) · Cell · doi:10.1016/j.cell.2011.10.002 · Cited by 2,187 · see citing works
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
Castello, A., Fischer, B., Eichelbaum, K., Horos, R., Beckmann, B. M., Strein, C., Davey, N. E., Humphreys, D. T., Preiss, T., Steinmetz, L. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.031 · Cited by 2,132 · see citing works
5′ UTR m6A Promotes Cap-Independent Translation
Meyer, K. D., Patil, D. P., Zhou, J. L., Zinoviev, A., Skabkin, M. A., Elemento, O., Pestova, T. V., Qian, S., & Jaffrey, S. R. (2015) · Cell · doi:10.1016/j.cell.2015.10.012 · Cited by 1,812 · see citing works
Feedback Inhibition of the Unfolded Protein Response by GADD34-Mediated Dephosphorylation of eIF2α
Novoa, I., Zeng, H., Harding, H. P., & Ron, D. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.1011 · Cited by 1,392 · see citing works
The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA
Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., Kol, N., Ben-Haim, M. S., Dai, Q., Segni, A. D., Salmon‐Divon, M., Clark, W. C., et al. (2016) · Nature · doi:10.1038/nature16998 · Cited by 1,026 · see citing works
Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA
Squires, J. E., Patel, H. R., Nousch, M., Sibbritt, T., Humphreys, D. T., Parker, B. J., Suter, C. M., & Preiß, T. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks144 · Cited by 1,011 · see citing works
Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells
Carlile, T. M., Rojas-Durán, M. F., Zinshteyn, B., Shin, H., Bartoli, K. M., & Gilbert, W. V. (2014) · Nature · doi:10.1038/nature13802 · Cited by 1,004 · see citing works
Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
Schwartz, S., Bernstein, D. A., Mumbach, M. R., Jovanović, M., Herbst, R. H., León-Ricardo, B. X., Engreitz, J., Guttman, M., Satija, R., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.028 · Cited by 1,001 · see citing works
Karikó, K., Muramatsu, H., Ludwig, J., & Weissman, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr695 · Cited by 898 · see citing works
The RNA modification database, RNAMDB: 2011 update
Cantara, W. A., Crain, P. F., Rozenski, J., McCloskey, J. A., Harris, K. A., Zhang, X., Vendeix, F. A. P., Fabris, D., & Agris, P. F. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1028 · Cited by 822 · see citing works
Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
Kormann, M. S. D., Hasenpusch, G., Aneja, M. K., Nica, G., Flemmer, A. W., Herber-Jonat, S., Huppmann, M., Mays, L. E., Illenyi, M., Schams, A., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1733 · Cited by 733 · see citing works
Andries, O., Mc Cafferty, S., De Smedt, S. C., Weiss, R., Sanders, N. N., & Kitada, T. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.051 · Cited by 701 · see citing works
Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome
Li, X., Xiong, X., Wang, K., Wang, L., Shu, X., Ma, S., & Yi, C. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2040 · Cited by 684 · see citing works
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation
Anderson, B. R., Muramatsu, H., Nallagatla, S. R., Bevilacqua, P. C., Sansing, L. H., Weissman, D., & Karikó, K. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq347 · Cited by 682 · see citing works
Zangi, L., Lui, K. O., von Gise, A., Ma, Q., Ebina, W., Ptaszek, L. M., Später, D., Xu, H., Tabebordbar, M., Gorbatov, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2682 · Cited by 646 · see citing works
Ribosome profiling: new views of translation, from single codons to genome scale
Ingolia, N. T. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3645 · Cited by 636 · see citing works
Yu, C., Dang, Y., Zhou, Z., Wu, C., Zhao, F., Sachs, M. S., & Liu, Y. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.018 · Cited by 605 · see citing works
Translation efficiency is determined by both codon bias and folding energy
Tuller, T., Waldman, Y. Y., Kupiec, M., & Ruppin, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909910107 · Cited by 584 · see citing works
Pseudouridine in RNA: What, Where, How, and Why
Charette, M., & Gray, M. W. (2000) · IUBMB Life · doi:10.1080/152165400410182 · Cited by 577 · see citing works
Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome
Li, X., Zhu, P., Ma, S., Song, J., Bai, J., Sun, F., & Yi, C. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1836 · Cited by 554 · see citing works
Kozak, M. (1997) · The EMBO Journal · doi:10.1093/emboj/16.9.2482 · Cited by 478 · see citing works
Ribosome pausing and stacking during translation of a eukaryotic mRNA.
Wolin, S. L., & Walter, P. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03233.x · Cited by 454 · see citing works
Cap and cap‐binding proteins in the control of gene expression
Topisirović, I., Svitkin, Y. V., Sonenberg, N., & Shatkin, A. J. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.52 · Cited by 402 · see citing works
Self-citationAnderson, B. R., Muramatsu, H., Jha, B. K., Silverman, R. H., Weissman, D., & Kariko, K. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr586 · Cited by 356 · see citing works
A pause for thought along the co-translational folding pathway
Komar, A. A. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.10.002 · Cited by 349 · see citing works
Functional complexity and regulation through RNA dynamics
Dethoff, E. A., Chugh, J., Mustoe, A. M., & Al‐Hashimi, H. M. (2012) · Nature · doi:10.1038/nature10885 · Cited by 331 · see citing works
New Insights into the Role of RNase L in Innate Immunity
Chakrabarti, A., Jha, B. K., & Silverman, R. H. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2010.0120 · Cited by 313 · see citing works
The exosome: a multipurpose RNA-decay machine
Schmid, M., & Jensen, T. H. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.07.003 · Cited by 259 · see citing works
Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation
Pop, C., Rouskin, S., Ingolia, N. T., Han, L., Phizicky, E. M., Weissman, J. S., & Koller, D. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145524 · Cited by 238 · see citing works
Pausing on Polyribosomes: Make Way for Elongation in Translational Control
Richter, J. D., & Coller, J. M. (2015) · Cell · doi:10.1016/j.cell.2015.09.041 · Cited by 204 · see citing works
Double-Stranded Poliovirus RNA Inhibits Initiation of Protein Synthesis by Reticulocyte Lysates
Ehrenfeld, E., & Hunt, T. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.5.1075 · Cited by 202 · see citing works
Edery, I., Petryshyn, R., & Sonenberg, N. (1989) · Cell · doi:10.1016/0092-8674(89)90904-5 · Cited by 196 · see citing works
Self-citationCarroll, K. L., Elroy‐Stein, O., Moss, B., & Jagus, R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31463-7 · Cited by 184 · see citing works
Merrick, W. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.675280 · Cited by 176 · see citing works
Dynamics of translation by single ribosomes through mRNA secondary structures
Chen, C., Zhang, H., Broitman, S. L., Reiche, M., Farrell, I., Cooperman, B. S., & Goldman, Y. E. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2544 · Cited by 147 · see citing works
Assembly and analysis of eukaryotic translation initiation complexes.
Pisarev, A., Unbehaun, A., Hellen, C., & Pestova, T. (2007) · Methods in Enzymology · doi:10.1016/s0076-6879(07)30007-4 · Cited by 141 · see citing works
Regulation of innate immunity through RNA structure and the protein kinase PKR
Nallagatla, S. R., Toroney, R., & Bevilacqua, P. C. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.11.003 · Cited by 133 · see citing works
Svitkin, Y., Herdy, B., Costa-Mattioli, M., Gingras, A., Raught, B., & Sonenberg, N. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10556-10565.2005 · Cited by 126 · see citing works
Self-citation1 Origins and Principles of Translational ControlPreprint
Mathews, M. B., Sonenberg, N., & Hershey, J. W. B. (2007) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969767.48.1 · Cited by 119 · see citing works
Self-citationThe role of fluctuations in tRNA selection by the ribosome
Lee, T.-H., Blanchard, S. C., Kim, H. D., Puglisi, J. D., & Chu, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705988104 · Cited by 102 · see citing works
Growth-related expression of a double-stranded RNA-dependent protein kinase in 3T3 cells.
Petryshyn, R., Chen, J. J., & London, I. M. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42664-0 · Cited by 91 · see citing works
Kopeina, G. S., Afonina, Z. A., Gromova, K. V., Shirokov, V. A., Vasiliev, V. D., & Spirin, A. S. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1177 · Cited by 81 · see citing works
Vassilenko, K. S., Alekhina, O. M., Dmitriev, S. E., Shatsky, I. N., & Spirin, A. S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr147 · Cited by 81 · see citing works
An Efficient System for Cap- and Poly(A)-Dependent Translation In Vitro
Svitkin, Y. V., & Sonenberg, N. (2004) · Humana Press eBooks · doi:10.1385/1-59259-750-5:155 · Cited by 80 · see citing works
Self-citationSoto‐Rifo, R., Ricci, E. P., Décimo, D., Moncorgé, O., & Ohlmann, T. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm682 · Cited by 79 · see citing works
General RNA‐binding proteins have a function in poly(A)‐binding protein‐dependent translation
Svitkin, Y. V., Evdokimova, V. M., Brasey, A., Pestova, T. V., Fantus, D., Yanagiya, A., Imataka, H., Skabkin, M. A., Ovchinnikov, L. P., Merrick, W. C., et al. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.259 · Cited by 74 · see citing works
Self-citationA hybridoma-based in vitro translation system that efficiently synthesizes glycoproteins
Mikami, S., Kobayashi, T., Yokoyama, S., & Imataka, H. (2006) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2006.06.018 · Cited by 68 · see citing works
Brand, R. C., Klootwijk, J., Planta, R. J., & Maden, B. E. H. (1978) · Biochemical Journal · doi:10.1042/bj1690071 · Cited by 65 · see citing works
Control of Translation and miRNA-Dependent Repression by a Novel Poly(A) Binding Protein, hnRNP-Q
Svitkin, Y. V., Yanagiya, A., Karetnikov, A., Alain, T., Fabian, M. R., Khoutorsky, A., Perreault, S., Topisirović, I., & Sonenberg, N. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001564 · Cited by 59 · see citing works
Self-citationZeenko, V. V., Wang, C., Majumder, M., Komar, A. A., Snider, M. D., Merrick, W. C., Kaufman, R. J., & Hatzoglou, M. (2008) · RNA · doi:10.1261/rna.825008 · Cited by 44 · see citing works
Conformation transitions of eukaryotic polyribosomes during multi-round translation
Afonina, Z. A., Myasnikov, A. G., Shirokov, V. A., Klaholz, B. P., & Spirin, A. S. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1270 · Cited by 41 · see citing works
Савинова, О. В., & Jagus, R. (1997) · Methods · doi:10.1006/meth.1996.0438 · Cited by 30 · see citing works
Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation
Fang, H., & Lyon, G. J. (2015) · Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) · Cited by 26 · see citing works
Mikami, S., Kobayashi, T., Machida, K., Masutani, M., Yokoyama, S., & Imataka, H. (2010) · Biotechnology Letters · doi:10.1007/s10529-010-0251-7 · Cited by 25 · see citing works
Time-dependent increase in ribosome processivity
Bonderoff, J. M., & Lloyd, R. E. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq566 · Cited by 24 · see citing works
Svitkin, Y. V., Pause, A., López‐Lastra, M., Perreault, S., & Sonenberg, N. (2005) · Journal of Virology · doi:10.1128/jvi.79.11.6868-6881.2005 · Cited by 15 · see citing works
Self-citationSvitkin, Y. V., & Sonenberg, N. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)29004-4 · Cited by 14 · see citing works
Self-citation
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Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 801 · see citing works
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656 · see citing works
Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering
Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C. H., & Mitchell, M. J. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b04246 · Cited by 636 · see citing works
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
mRNA structure regulates protein expression through changes in functional half-life
Mauger, D. M., Cabral, B. J., Presnyak, V., Su, S. V., Reid, D. W., Goodman, B., Link, K., Khatwani, N., Reynders, J., Moore, M. J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908052116 · Cited by 555 · see citing works
Self-citationmRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.020 · Cited by 507 · see citing works
RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo
Wesselhoeft, R. A., Kowalski, P. S., Parker-Hale, F. C., Huang, Y., Bisaria, N., & Anderson, D. G. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.02.015 · Cited by 482 · see citing works
Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines
Nance, K. D., & Meier, J. L. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00197 · Cited by 466 · see citing works
Parayath, N. N., Stephan, S. B., Koehne, A. L., Nelson, P. S., & Stephan, M. T. (2020) · Nature Communications · doi:10.1038/s41467-020-19486-2 · Cited by 447 · see citing works
RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges
Yu, A., Choi, Y. H., & Tu, M. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019554 · Cited by 405 · see citing works
RNA modifications in physiology and disease: towards clinical applications
Delaunay, S., Helm, M., & Frye, M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00645-2 · Cited by 358 · see citing works
A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development
Li, Y., Tenchov, R., Smoot, J., Liu, C., Watkins, S., & Zhou, Q. A. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00120 · Cited by 345 · see citing works
Suzuki, Y., & Ishihara, H. (2021) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100424 · Cited by 304 · see citing works
The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines
Morais, P., Adachi, H., & Yu, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.789427 · Cited by 274 · see citing works
Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents
Blanchard, E. L., Vanover, D., Bawage, S., Tiwari, P., Rotolo, L., Beyersdorf, J. P., Peck, H., Bruno, N. C., Hincapie, R., Michel, F., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00822-w · Cited by 212 · see citing works
mRNA vaccines for infectious diseases — advances, challenges and opportunities
Pardi, N., & Krammer, F. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01042-y · Cited by 246 · see citing works
An RNA toolbox for cancer immunotherapy
Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.132 · Cited by 229 · see citing works
Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives
Gómez-Aguado, I., Rodríguez-Castejón, J., Vicente-Pascual, M., Rodríguez‐Gascón, A., Solinís, M. Á., & del Pozo‐Rodríguez, A. (2020) · Nanomaterials · doi:10.3390/nano10020364 · Cited by 224 · see citing works
N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting
Mulroney, T. E., Pöyry, T. A. A., Yam‐Puc, J. C., Rust, M. A., Harvey, R. F., Kalmár, L., Horner, E. C., Booth, L. H., Ferreira, A., Stoneley, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06800-3 · Cited by 232 · see citing works
Xue, L., Gong, N., Shepherd, S. J., Xiong, X., Liao, X., Han, X., Zhao, G., Song, C., Huang, X., Zhang, H., et al. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c02706 · Cited by 189 · see citing works
Nucleic acid drugs: recent progress and future perspectives
Sun, X., Setrerrahmane, S., Li, C., Hu, J., & Xu, H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02035-4 · Cited by 202 · see citing works
Carlsson, L. G., Clarke, J. C., Yen, C. Y. T., Gregoire, F. M., Albery, T., Billger, M. A., Egnell, A., Gan, L., Jennbacken, K., Johansson, E., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.04.003 · Cited by 180 · see citing works
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Van der Jeught, K., De Koker, S., Bialkowski, L., Heirman, C., Tjok Joe, P., Perche, F., Maenhout, S., Bevers, S., Broos, K., Deswarte, K., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b00966 · Cited by 139 · see citing works
Immunogenicity of In Vitro -Transcribed RNA
Mu, X. N., & Hur, S. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00521 · Cited by 138 · see citing works
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Dhaliwal, H. K., Fan, Y., Kim, J., & Amiji, M. M. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00170 · Cited by 136 · see citing works
Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines
Rijkers, G. T., Weterings, N., Obregón‐Henao, A., Dutt, T., Dutt, T. S., van Overveld, F. J., & Henao-Tamayo, M. I. (2021) · Vaccines · doi:10.3390/vaccines9080848 · Cited by 134 · see citing works
Amplifying gene expression with RNA-targeted therapeutics
Khorkova, O., Stahl, J., Joji, A., Volmar, C., & Wahlestedt, C. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00704-7 · Cited by 132 · see citing works
N 1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells
Parr, C., Wada, S., Kotake, K., Kameda, S., Matsuura, S., Sakashita, S., Park, S., Sugiyama, H., Kuang, Y., & Saito, H. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa070 · Cited by 121 · see citing works
Microfluidic fabrication of lipid nanoparticles for the delivery of nucleic acids
Prakash, G., Shokr, A., Willemen, N. G. A., Bashir, S. M., Shin, S. R., & Hassan, S. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114197 · Cited by 117 · see citing works
Sayers, E. J., Peel, S. E., Schantz, A., England, R., Beano, M., Bates, S. M., Desai, A. S., Puri, S., Ashford, M. B., & Jones, A. T. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.07.018 · Cited by 117 · see citing works
Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations
Hetherington, I., & Totary-Jain, H. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.08.024 · Cited by 116 · see citing works
Recent Developments in mRNA-Based Protein Supplementation Therapy to Target Lung Diseases
Sahu, I., Haque, A. K. M. A., Weidensee, B., Weinmann, P., & Kormann, M. S. D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.019 · Cited by 104 · see citing works
Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications
Patel, S., Athirasala, A., Menezes, P. D. P., Ashwanikumar, N., Zou, T., Sahay, G., & Bertassoni, L. E. (2018) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0444 · Cited by 99 · see citing works
Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery
Melamed, J. R., Hajj, K. A., Chaudhary, N., Strelkova, D., Arral, M. L., Pardi, N., Alameh, M., Miller, J. B., Farbiak, L., Siegwart, D. J., et al. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.11.022 · Cited by 98 · see citing works
Advancements of in vitro transcribed mRNA (IVT mRNA) to enable translation into the clinics
Kang, D. D., Li, H., & Dong, Y. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114961 · Cited by 100 · see citing works
The Pivotal Role of Chemical Modifications in mRNA Therapeutics
Liu, A., & Wang, X. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.901510 · Cited by 97 · see citing works
Synthetic modified messenger RNA for therapeutic applications
Gao, M., Zhang, Q., Feng, X.-H., & Liu, J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.06.020 · Cited by 89 · see citing works
A New Era for Rare Genetic Diseases: Messenger RNA Therapy
Martini, P. G. V., & Guey, L. T. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.090 · Cited by 88 · see citing works
Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination
Yu, A., & Tu, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107967 · Cited by 88 · see citing works
Advancements in mRNA Encoded Antibodies for Passive Immunotherapy
Deal, C. E., Carfı́, A., & Plante, O. J. (2021) · Vaccines · doi:10.3390/vaccines9020108 · Cited by 87 · see citing works
Ripoll, M., Bernard, M., Vaure, C., Bazin, E., Commandeur, S., Perkov, V., Lemdani, K., Nicolaï, M., Bonifassi, P., Kichler, A., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121570 · Cited by 85 · see citing works
mRNA in cancer immunotherapy: beyond a source of antigen
Hoecke, L. V., Verbeke, R., Dewitte, H., Lentacker, I., Vermaelen, K. Y., Breckpot, K., & Lint, S. V. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01329-3 · Cited by 80 · see citing works
Potentialities and Challenges of mRNA Vaccine in Cancer Immunotherapy
Duan, L.-J., Wang, Q., Zhang, C., Yang, D.-X., & Zhang, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.923647 · Cited by 79 · see citing works
Moradian, H., Roch, T., Anthofer, L., Lendlein, A., & Gossen, M. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.01.004 · Cited by 75 · see citing works
N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation
Monroe, J. G., Eyler, D. E., Mitchell, L., Deb, I., Bojanowski, A., Srinivas, P., Dunham, C. M., Roy, B., Frank, A. T., & Koutmou, K. S. (2024) · Nature Communications · doi:10.1038/s41467-024-51301-0 · Cited by 77 · see citing works
Post-transcriptional control of gene expression following stress: the role of RNA-binding proteins
Harvey, R. F., Dezi, V., Pizzinga, M., & Willis, A. E. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160364 · Cited by 73 · see citing works
Liu, J., Zhang, Y., Liu, C., Jiang, Y., Wang, Z., Guo, Z., & Li, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.07.018 · Cited by 73 · see citing works
Translation—A tug of war during viral infection
Rozman, B., Fisher, T., & Stern‐Ginossar, N. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.10.012 · Cited by 72 · see citing works
Delivery of therapeutic oligonucleotides in nanoscale
Wu, L., Zhou, W., Lin, L., Chen, A., Feng, J. C., Qu, X., Zhang, H., & Yue, J. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.05.038 · Cited by 70 · see citing works
Chu, J.-M., Ye, T.-T., Ma, C.-J., Lan, M., Liu, T., Yuan, B., & Feng, Y. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00906 · Cited by 70 · see citing works
Strzelecka, D., Śmietański, M., Sikorski, P. J., Warmiński, M., Kowalska, J., & Jemielity, J. (2020) · RNA · doi:10.1261/rna.077099.120 · Cited by 67 · see citing works
Simultaneous nanopore profiling of mRNA m6A and pseudouridine reveals translation coordination
Huang, S., Wylder, A. C., & Pan, T. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02135-0 · Cited by 65 · see citing works
Makkar, S. K. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1675209 · Cited by 65 · see citing works
N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products
Kim, K. Q., Burgute, B. D., Tzeng, S., Jing, C., Jungers, C. F., Zhang, J., Yan, L. L., Vierstra, R. D., Djuranović, S., Evans, B. S., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111300 · Cited by 68 · see citing works
mRNA-Based Therapeutics in Cancer Treatment
Sun, H., Zhang, Y., Wang, G., Yang, W., & Xu, Y. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020622 · Cited by 63 · see citing works
Bernard, M., Bazin, E., Petiot, N., Lemdani, K., Commandeur, S., Verdelet, C., Margot, S., Perkov, V., Ripoll, M., Garinot, M., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.05.004 · Cited by 62 · see citing works
Lyu, X., Yang, Q., Zhao, F.-Z., & Liu, Y. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab729 · Cited by 62 · see citing works
The vasculature: a therapeutic target in heart failure?
Luxán, G., & Dimmeler, S. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab047 · Cited by 58 · see citing works
Wu, H., Peng, Z., Xu, Y., Sheng, Z., Liu, Y., Liao, Y., Wang, Y., Wen, Y., Yi, J., Xie, C., et al. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02695-x · Cited by 59 · see citing works
Bérouti, M., Wagner, M., Greulich, W., Piseddu, I., Gärtig, J., Hansbauer, L., Müller-Hermes, C., Heiß, M., Pichler, A., Tölke, A. J., et al. (2025) · Cell · doi:10.1016/j.cell.2025.05.032 · Cited by 63 · see citing works
A Review on the Stability Challenges of Advanced Biologic Therapeutics
Sarvepalli, S., Pasika, S. R., Verma, V., Thumma, A., Bolla, S., Nukala, P. K., Butreddy, A., & Bolla, P. K. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17050550 · Cited by 58 · see citing works
Human RNase 4 improves mRNA sequence characterization by LC–MS/MS
Wolf, E. J., Grünberg, S., Dai, N., Chen, T.-H., Roy, B., Yigit, E., & Junior, I. R. C. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac632 · Cited by 53 · see citing works
Lin, S., & Kuang, M. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00884-y · Cited by 52 · see citing works
An Update on mRNA-Based Viral Vaccines
Jeeva, S., Kim, K., Shin, C. H., Wang, B., & Kang, S. (2021) · Vaccines · doi:10.3390/vaccines9090965 · Cited by 49 · see citing works
The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics
Muslimov, A. R., Tereshchenko, V., Shevyrev, D., Rogova, A. S., Lepik, K. V., Reshetnikov, V. V., & Ivanov, R. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914820 · Cited by 50 · see citing works
Exogenous RNA surveillance by proton-sensing TRIM25
Kim, M., Pyo, Y., Hyun, S., Jeong, M., Choi, Y., & Kim, V. N. (2025) · Science · doi:10.1126/science.ads4539 · Cited by 49 · see citing works
mRNA Vaccines: Why Is the Biology of Retroposition Ignored?
Domazet‐Lošo, T. (2022) · Genes · doi:10.3390/genes13050719 · Cited by 44 · see citing works
Tang, X., Huo, M., Chen, Y., Huang, H., Qin, S., Luo, J., Qin, Z., Jiang, X., Liu, Y., Duan, X., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.11.003 · Cited by 47 · see citing works
Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression
Kramer, N. J., Prakash, G., Isaac, R. S., Choquet, K., Soto, I. C., Petrova, B., Merens, H. E., Kanarek, N., & Churchman, L. S. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01244-3 · Cited by 44 · see citing works
Dobrovolskaia, M. A., & Bathe, M. (2020) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1657 · Cited by 44 · see citing works
Steinle, H., Weber, M., Behring, A., Mau-Holzmann, U. A., OHLE, C. V., Popov, A., Schlensak, C., Wendel, H. P., & Avci‐Adali, M. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.07.016 · Cited by 43 · see citing works
Thatte, A. S., Hamilton, A. G., Nachod, B. E., Mukalel, A. J., Billingsley, M. M., Palanki, R., Swingle, K. L., & Mitchell, M. J. (2023) · Nano Letters · doi:10.1021/acs.nanolett.3c02573 · Cited by 44 · see citing works
Chemical modifications to mRNA nucleobases impact translation elongation and termination
Franco, M. K., & Koutmou, K. S. (2022) · Biophysical Chemistry · doi:10.1016/j.bpc.2022.106780 · Cited by 43 · see citing works
Stronger together for in-cell translation: natural and unnatural base modified mRNA
Bornewasser, L., Domnick, C., & Kath‐Schorr, S. (2022) · Chemical Science · doi:10.1039/d2sc00670g · Cited by 42 · see citing works
N1-methyl-pseudouridine is incorporated with higher fidelity than pseudouridine in synthetic RNAs
Chen, T.-H., Potapov, V., Dai, N., Ong, J. L., & Roy, B. (2022) · Scientific Reports · doi:10.1038/s41598-022-17249-1 · Cited by 43 · see citing works
Optimizing Modified mRNA In Vitro Synthesis Protocol for Heart Gene Therapy
Hadas, Y., Sultana, N., Youssef, E., Sharkar, M. T. K., Kaur, K., Chepurko, E., & Zangi, L. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.07.006 · Cited by 41 · see citing works
Pseudouridines in RNAs: switching atoms means shifting paradigms
Lin, T., Mehta, R., & Glatt, S. (2021) · FEBS Letters · doi:10.1002/1873-3468.14188 · Cited by 41 · see citing works
Delivery of synthetic mRNAs for tissue regeneration
Steinle, H., Weber, M., Stoppelkamp, S., Große‐Berkenbusch, K., Golombek, S., Weber, M., Çanak-Ipek, T., Trenz, S.-M., Schlensak, C., & Avci‐Adali, M. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114007 · Cited by 41 · see citing works
Miller, J. B., & Siegwart, D. J. (2018) · Nano Research · doi:10.1007/s12274-018-2099-4 · Cited by 40 · see citing works
A Census and Categorization Method of Epitranscriptomic Marks
Mathlin, J., Pera, L. L., & Colombo, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134684 · Cited by 40 · see citing works
The Epitranscriptome in Translation RegulationPreprint
Peer, E., Moshitch-Moshkovitz, S., Rechavi, G., & Dominissini, D. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032623 · Cited by 40 · see citing works
Strong Immune Responses Induced by Direct Local Injections of Modified mRNA-Lipid Nanocomplexes
Arya, S., Lin, Q., Zhou, N., Gao, X., & Huang, J.-D. (2020) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2019.12.044 · Cited by 39 · see citing works
The potential of mRNA vaccines in cancer nanomedicine and immunotherapy
Pan, S., Fan, R., Han, B. R., Tong, A., & Guo, G. F. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.11.003 · Cited by 39 · see citing works
Tumor-activated IL-2 mRNA delivered by lipid nanoparticles for cancer immunotherapy
Jiang, Y., Zhang, Y., Liu, C., Liu, J., Xue, W., Wang, Z., & Li, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.03.016 · Cited by 38 · see citing works
Nakanishi, H., Yoshii, T., Kawasaki, S., Hayashi, K., Tsutsui, K., Oki, C., Tsukiji, S., & Saito, H. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2021.01.002 · Cited by 38 · see citing works
McErlean, E., & McCarthy, H. O. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02746-4 · Cited by 33 · see citing works
RNA-based therapy for osteogenesis
Wang, P., Perche, F., Logeart‐Avramoglou, D., & Pichon, C. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118594 · Cited by 37 · see citing works
Regulatory Considerations on the Development of mRNA Vaccines
Naik, R., & Peden, K. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_220 · Cited by 37 · see citing works
Svitkin, Y. V., Gingras, A., & Sonenberg, N. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1241 · Cited by 37 · see citing works
Self-citationDemystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases
Rouf, N. Z., Biswas, S., Tarannum, N., Oishee, L. M., & Muna, M. M. (2022) · RNA Biology · doi:10.1080/15476286.2022.2055923 · Cited by 36 · see citing works
Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
Yang, W., Cao, J., Cheng, H., Chen, L., Yu, M., Chen, Y., & Cui, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.11.014 · Cited by 36 · see citing works
Effects of mRNA Modifications on Translation: An Overview
Roy, B. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1374-0_20 · Cited by 35 · see citing works
Selective Xi reactivation and alternative methods to restore MECP2 function in Rett syndrome
Grimm, N.-B., & Lee, J. T. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.01.007 · Cited by 33 · see citing works
Synthesis of point-modified mRNA
Hertler, J., Slama, K., Schober, B., Özrendeci, Z., Marchand, V., Motorin, Y., & Helm, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac719 · Cited by 35 · see citing works
RNase H-based analysis of synthetic mRNA 5′ cap incorporation
Chan, S., Whipple, J. M., Dai, N., Kelley, T. M., Withers, K., Tzertzinis, G., Junior, I. R. C., & Robb, G. B. (2022) · RNA · doi:10.1261/rna.079173.122 · Cited by 33 · see citing works
Nakanishi, H., & Saito, H. (2020) · Nature Communications · doi:10.1038/s41467-020-15061-x · Cited by 32 · see citing works
- Authors
- Svitkin, Y. V., Cheng, Y. M., Chakraborty, T., Presnyak, V., John, M., & Sonenberg, N.
- Affiliations
- Institut du cancer Rosalind & Morris Goodman (CA)
- Moderna Therapeutics (United States) (US)
- Corresponding author
- Svitkin, Yuri V.
- Sonenberg, Nahum
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-02-23
- Volume
- 45
- Issue
- 10
- Pages
- 6023-6036
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC5449617
- OpenAlex
- W2589945527
- Cited by
- 278
- References
- 63
- Citations by year
- 2026: 38 · 2025: 49 · 2024: 31 · 2023: 32 · 2022: 48 · 2021: 29 · 2020: 22 · 2019: 13 · 2018: 13 · 2017: 2
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- nucleoside-modified mRNA, translation efficiency, eIF2α phosphorylation, ribosome density, ribosome pausing, ribosome recycling, in vitro translation, in vitro transcribed mRNA
- MeSH terms
- Animals, Cell Line, Cell-Free System, Enzyme Activation, Fibroblasts, HeLa Cells, Humans, Phosphorylation, Polyribosomes, Protein Processing, Post-Translational, Pseudouridine, RNA, RNA, Messenger, Transfection, Protein Biosynthesis, Eukaryotic Initiation Factor-2, eIF-2 Kinase, RNA Stability, Mice, HEK293 Cells
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