Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics: Getting the message across

Minnaert, An-Katrien; Vanluchene, Helena; Verbeke, Rein; Lentacker, Ine; De Smedt, Stefaan C.; Raemdonck, Koen; Sanders, Niek N.; Remaut, Katrien

doi:10.1016/j.addr.2021.113900

Cited by 157RNA Interference and Gene DeliveryImmunotherapy and Immune ResponsesRNA and protein synthesis mechanisms

Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics: Getting the message across

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Minnaert, An-Katrien, Vanluchene, Helena, Verbeke, Rein, Lentacker, Ine, De Smedt, Stefaan C., Raemdonck, Koen, Sanders, Niek N., Remaut, Katrien·2021·Advanced Drug Delivery Reviews

DOI 10.1016/j.addr.2021.113900PMC PMC8325057

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Abstract

The recent approval of messenger RNA (mRNA)-based vaccines to combat the SARS-CoV-2 pandemic highlights the potential of both conventional mRNA and self-amplifying mRNA (saRNA) as a flexible immunotherapy platform to treat infectious diseases. Besides the antigen it encodes, mRNA itself has an immune-stimulating activity that can contribute to vaccine efficacy. This self-adjuvant effect, however, will interfere with mRNA translation and may influence the desired therapeutic outcome. To further exploit its potential as a versatile therapeutic platform, it will be crucial to control mRNA's innate immune-stimulating properties. In this regard, we describe the mechanisms behind the innate immune recognition of mRNA and provide an extensive overview of strategies to control its innate immune-stimulating activity. These strategies range from modifications to the mRNA backbone itself, optimization of production and purification processes to the combination with innate immune inhibitors. Furthermore, we discuss the delicate balance of the self-adjuvant effect in mRNA vaccination strategies, which can be both beneficial and detrimental to the therapeutic outcome.

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The current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy.
“However, the current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy, as reported by multiple independent groups5,19–28.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [5]
The ‘Modifications to the mRNA backbone itself’ section says modified nucleosides are expected to impair saRNA self-replication, and the Conclusions say nucleoside modification is not tolerated if saRNA functionality is to be retained (page numbers unavailable). The paper does not establish that modified NTPs abrogate downstream efficacy or report that this result was demonstrated by multiple independent groups. (LLM, conf=0.85)
Experimental — accuracy not yet measured
saRNAs use an RNA-dependent RNA polymerase from an alphavirus and conserved sequence elements at the 5′ and 3′ ends for replication, leading to robust and durable expression of encoded protein cargo.
“saRNAs use an RNA-dependent RNA polymerase from an alphavirus and the corresponding conserved sequence elements at the 5′ and 3′ ends for replication, leading to robust and durable expression of encoded protein cargo5–7.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [5]
The “Self-amplifying mRNA” section says most saRNAs are alphavirus-based, identifies nsP4 as an RNA-dependent RNA polymerase, and reports higher, longer-lasting protein expression from self-replication. It describes 5′ and 3′ UTRs and replication promoters, but does not identify conserved sequence elements at both ends as required for replication. (LLM, conf=0.86)
Experimental — accuracy not yet measured
The early and intense type I IFN response induced by saRNA detection hinders replication and antigen expression.
“The early and intense type I IFN response induced by saRNA detection hinders replication and antigen expression, similar to unmodified mRNA5,13–15.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [5]
In “Type I IFN-mediated effects: Beneficial or detrimental for mRNA vaccines?” (page unavailable), the review reports that an early, robust type I IFN response to a saRNA vaccine in mice negatively affected initial antigen expression. It does not establish in that passage that the response hindered saRNA replication; the “Innate immunity stimulation” section describes antiviral mechanisms generally, without making that specific link. (LLM, conf=0.84)
Experimental — accuracy not yet measured

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · see citing works
Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose
Aviv, H., & Leder, P. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.6.1408 · Cited by 6,636 · see citing works
mRNA vaccines — a new era in vaccinology
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667 · see citing works
Direct Gene Transfer into Mouse Muscle in Vivo
Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., & Felgner, P. L. (1990) · Science · doi:10.1126/science.1690918 · Cited by 4,173 · see citing works
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S. (2004) · Science · doi:10.1126/science.1093620 · Cited by 3,947 · see citing works
Mechanisms of type-I- and type-II-interferon-mediated signalling
Platanias, L. C. (2005) · Nature reviews. Immunology · doi:10.1038/nri1604 · Cited by 3,480 · see citing works
Regulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,311 · see citing works
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067 · see citing works
Type I interferons in infectious disease
McNab, F., Mayer-Barber, K., Sher, A., Wack, A., & O'Garra, A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3787 · Cited by 2,780 · see citing works
Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728 · see citing works
Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA
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
Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates.
Milligan, J., Groebe, D., Witherell, G. W., & Uhlenbeck, O. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.21.8783 · Cited by 1,971 · see citing works
Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability
Karikó, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S., & Weissman, D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.200 · Cited by 1,930 · see citing works
Systemic 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 1,771 · see citing works
Codon bias and heterologous protein expression
Gustafsson, C., Govindarajan, S., & Minshull, J. (2004) · Trends in Biotechnology · doi:10.1016/j.tibtech.2004.04.006 · Cited by 1,330 · see citing works
An Unstable Intermediate Carrying Information from Genes to Ribosomes for Protein Synthesis
Brenner, S., Jacob, F., & Meselson, M. S. (1961) · Nature · doi:10.1038/190576a0 · Cited by 1,235 · see citing works
The ins and outs of MHC class II-mediated antigen processing and presentation
Roche, P. A., & Furuta, K. (2015) · Nature reviews. Immunology · doi:10.1038/nri3818 · Cited by 1,207 · see citing works
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
Surface chromium on Terracotta Army bronze weapons is neither an ancient anti-rust treatment nor the reason for their good preservation
Martinón‐Torres, M., Li, X. J., Xia, Y., Benzonelli, A., Bevan, A., Ma, S., Huang, J., Wang, L., Lan, D., Liu, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-40613-7 · Cited by 1,090 · see citing works
Translational control by 5′-untranslated regions of eukaryotic mRNAs
Hinnebusch, A. G., Ivanov, I. P., & Sonenberg, N. (2016) · Science · doi:10.1126/science.aad9868 · Cited by 1,079 · see citing works
An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
Sahin, U., Oehm, P., Derhovanessian, E., Jabulowsky, R. A., Vormehr, M., Gold, M., Maurus, D., Schwarck-Kokarakis, D., Kuhn, A. N., Omokoko, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2537-9 · Cited by 1,052 · see citing works
Quantitative assessment on the cloning efficiencies of lentiviral transfer vectors with a unique clone site
Zhang, G., & Tandon, A. (2012) · Scientific Reports · doi:10.1038/srep00415 · Cited by 1,039 · see citing works
Type I Interferons Potently Enhance Humoral Immunity and Can Promote Isotype Switching by Stimulating Dendritic Cells In Vivo
Bon, A. L., Schiavoni, G., D’Agostino, G., Gresser, I., Belardelli, F., & Tough, D. F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00126-1 · Cited by 973 · see citing works
Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines
Hassett, K. J., Benenato, K. E., Jacquinet, E., Lee, A., Woods, A., Yuzhakov, O., Himansu, S., Deterling, J., Geilich, B. M., Ketova, T., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.01.013 · Cited by 927 · see citing works
2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members
Daffis, S., Szretter, K. J., Schriewer, J. M., Li, J., Youn, S., Errett, J. S., Lin, T., Schneller, S. W., Züst, R., Dong, H., et al. (2010) · Nature · doi:10.1038/nature09489 · Cited by 910 · see citing works
Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA
Karikó, K., Muramatsu, H., Ludwig, J., & Weissman, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr695 · Cited by 898 · see citing works
mRNA capping: biological functions and applications
Ramanathan, A., Robb, G. B., & Chan, S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw551 · Cited by 892 · see citing works
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Turner, J. S., O’Halloran, J. A., Kalaidina, E., Kim, W., Schmitz, A. J., Zhou, J. Q., Lei, T., Thapa, M., Chen, R. E., Case, J. B., et al. (2021) · Nature · doi:10.1038/s41586-021-03738-2 · Cited by 831 · see citing works
Codon optimality, bias and usage in translation and mRNA decay
Hanson, G., & Coller, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.91 · Cited by 825 · see citing works
Keeping It All Going—Complement Meets Metabolism
Kolev, M. V., & Kemper, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00001 · Cited by 819 · see citing works
Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
Züst, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B. W., Ziebuhr, J., Szretter, K. J., Baker, S. C., Barchet, W., Diamond, M. S., et al. (2011) · Nature Immunology · doi:10.1038/ni.1979 · Cited by 811 · see citing works
A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.
Noelle, R. J., Roy, M., Shepherd, D. M., Stamenkovic, I., Ledbetter, J. A., & Aruffo, A. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.14.6550 · Cited by 805 · see citing works
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
Activation of innate immune antiviral responses by Nod2
Sabbah, A., Chang, T. H., Harnack, R., Frohlich, V. C., Tominaga, K., Dube, P. H., Xiang, Y., & Bose, S. (2009) · Nature Immunology · doi:10.1038/ni.1782 · Cited by 754 · see citing works
Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
Saito, T., Owen, D. M., Jiang, F., Marcotrigiano, J., & Gale, M. (2008) · Nature · doi:10.1038/nature07106 · Cited by 745 · 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
Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy
Oberli, M. A., Reichmuth, A. M., Dorkin, J. R., Mitchell, M. J., Fenton, O. S., Jaklenec, A., Anderson, D. G., Langer, R., & Blankschtein, D. (2017) · Nano Letters · doi:10.1021/acs.nanolett.6b03329 · Cited by 719 · see citing works
N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice
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
Self-citation
Influences of mRNA secondary structure on initiation by eukaryotic ribosomes.
Kozak, M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.9.2850 · Cited by 687 · 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
Advances in mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 680 · see citing works
Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant
Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M. F., de Matos, I. G., Kluger, C., Salazar, A. Μ., Colonna, M., & Steinman, R. M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090247 · Cited by 663 · see citing works
Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction
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
Cutting Edge: Type I IFNs Provide a Third Signal to CD8 T Cells to Stimulate Clonal Expansion and Differentiation
Curtsinger, J., Valenzuela, J. O., Agarwal, P., Lins, D. C., & Mescher, M. F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4465 · Cited by 633 · see citing works
Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells
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 · see citing works
Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements
Barrett, L. W., Fletcher, S., & Wilton, S. D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0990-9 · Cited by 603 · see citing works
Vitamin D Is Required for ILC3 Derived IL-22 and Protection From Citrobacter rodentium Infection
Lin, Y., Arora, J., Diehl, K. C., Bora, S. A., & Cantorna, M. T. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00001 · Cited by 602 · see citing works
A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA
Baiersdörfer, M., Boros, G., Muramatsu, H., Mahiny, A., Vlatkovic, I., Sahin, U., & Karikó, K. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.02.018 · Cited by 569 · see citing works
COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines.
Meo, S. A., Bukhari, I. A., Akram, J., Meo, A. S., & Klonoff, D. C. (2021) · PubMed · doi:10.26355/eurrev_202102_24877 · Cited by 564 · 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
G-quadruplexes: a promising target for cancer therapy
Kosiol, N., Juranek, S., Brossart, P., Heine, A., & Paeschke, K. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01328-4 · Cited by 540 · see citing works
Complex modulation of cell type-specific signaling in response to type I interferons
van Boxel-Dezaire, A. H. H., Rani, M. R. S., & Stark, G. R. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.014 · Cited by 530 · see citing works
A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., et al. (2021) · Science · doi:10.1126/science.aay3638 · Cited by 520 · see citing works
Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals
Thess, A., Grund, S., Mui, B. L., Hope, M. J., Baumhof, P., Fotin-Mleczek, M., & Schlake, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.103 · Cited by 513 · cited 5× · see citing works
“[76] and viral UTRs from VEEV [77] and SINV [78].”
Influential
Recent advances in mRNA vaccine technology
Pardi, N., Hogan, M. J., & Weissman, D. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.01.008 · Cited by 512 · see citing works
mRNA 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
The dawn of mRNA vaccines: the COVID-19 case
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.03.043 · Cited by 504 · see citing works
Self-citation
Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses
Vogel, A. B., Lambert, L., Kinnear, E., Busse, D., Erbar, S., Reuter, K. C., Wicke, L., Perkovic, M., Beissert, T., Haas, H., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.11.017 · Cited by 501 · see citing works
Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species soecificity
Symons, J. A., Alcamı́, A., & Smith, G. L. (1995) · Cell · doi:10.1016/0092-8674(95)90076-4 · Cited by 491 · see citing works
Self-amplifying RNA vaccines for infectious diseases
Bloom, K., van den Berg, F., & Arbuthnot, P. (2021) · Gene Therapy · doi:10.1038/s41434-020-00204-y · Cited by 487 · see citing works
Regulation of antiviral T cell responses by type I interferons
Crouse, J., Kalinke, U., & Oxenius, A. (2015) · Nature reviews. Immunology · doi:10.1038/nri3806 · Cited by 480 · see citing works
High Guanine and Cytosine Content Increases mRNA Levels in Mammalian Cells
Kudla, G., Lipinski, L., Caffin, F., Helwak, A., & Zylicz, M. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040180 · Cited by 476 · see citing works
Role of 5′‐ and 3′‐untranslated regions of mRNAs in human diseases
Chatterjee, S., & Pal, J. K. (2009) · Biology of the Cell · doi:10.1042/bc20080104 · Cited by 439 · see citing works
Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination
Tam, H. H., Melo, M. B., Kang, M., Pelet, J. M., Ruda, V. M., Foley, M. H., Hu, J. K., Kumari, S., Crampton, J., Baldeon, A. D., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606050113 · Cited by 425 · see citing works
The challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28776-w · Cited by 399 · see citing works
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2021) · doi:10.1101/2021.03.29.437587 · Cited by 399 · see citing works
SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation
Lederer, K., Castaño, D., Gómez Atria, D., Oguin, T. H., Wang, S., Manzoni, T. B., Muramatsu, H., Hogan, M. J., Amanat, F., Cherubin, P., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.009 · Cited by 383 · cited 1× · see citing works
“demonstrated that intramuscular immunization with a SARS-CoV-2 (m1Ψ) mRNA-LNP vaccine in mice induced robust spike-specific GC B cells and follicular CD4+ T cell responses [217].”
Background
Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response
Linares-Fernández, S., Lacroix, C., Exposito, J.-Y., & Verrier, B. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.10.002 · Cited by 376 · see citing works
Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3′ UTRs Identified by Cellular Library Screening
Orlandini von Niessen, A. G., Poleganov, M. A., Rechner, C., Plaschke, A., Kranz, L. M., Fesser, S., Diken, M., Löwer, M., Vallazza, B., Beissert, T., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.12.011 · Cited by 365 · see citing works
Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity
Smith, G. L., Benfield, C. T. O., de Motes, C. M., Mazzon, M., Ember, S. W., Ferguson, B. J., & Sumner, R. P. (2013) · Journal of General Virology · doi:10.1099/vir.0.055921-0 · Cited by 359 · see citing works
Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I
Devarkar, S. C., Wang, C., Miller, M. T., Ramanathan, A., Jiang, F., Khan, A. G., Patel, S. S., & Marcotrigiano, J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515152113 · Cited by 357 · see citing works
Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L
Anderson, 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 Role for Codon Order in Translation Dynamics
Cannarozzi, G., Schraudolph, N. N., Faty, M., von Rohr, P., Friberg, M. T., Roth, A. C., Gonnet, P., Gonnet, G., & Barral, Y. (2010) · Cell · doi:10.1016/j.cell.2010.02.036 · Cited by 354 · see citing works
Impact of mRNA chemistry and manufacturing process on innate immune activation
Nelson, J., Sorensen, E. W., Mintri, S., Rabideau, A. E., Zheng, W., Besin, G., Khatwani, N., Su, S. V., Miracco, E. J., Issa, W. J., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz6893 · Cited by 354 · see citing works
A critical analysis of codon optimization in human therapeutics
Mauro, V. P., & Chappell, S. A. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.09.003 · Cited by 343 · see citing works
Untitled work
(2001) · PubMed Central · Cited by 342 · see citing works
Three decades of messenger RNA vaccine development
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2019) · Nano Today · doi:10.1016/j.nantod.2019.100766 · Cited by 342 · see citing works
Self-citation
A Cationic Nanoemulsion for the Delivery of Next-generation RNA Vaccines
Brito, L. A., Chan, M., Shaw, C. A., Hekele, A., Carsillo, T., Schaefer, M., Archer, J., Seubert, A., Otten, G. R., Beard, C. W., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.133 · Cited by 338 · see citing works
Activation of Innate Immunity Is Required for Efficient Nuclear Reprogramming
Lee, J., Sayed, N., Hunter, A. L., Au, K. F., Wong, W. H., Mocarski, E. S., Pera, R. A. R., Yakubov, E., & Cooke, J. P. (2012) · Cell · doi:10.1016/j.cell.2012.09.034 · Cited by 338 · see citing works
Efficient generation of human iPSCs by a synthetic self-replicative RNA
Yoshioka, N., Gros, E., Li, H.-R., Kumar, S., Deacon, D. C., Maron, C., Muotri, A. R., Chi, N. C., Fu, X.-D., Yu, B. D., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.06.001 · Cited by 312 · see citing works
Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma
Wilgenhof, S., Corthals, J., Heirman, C., van Baren, N., Lucas, S., Kvistborg, P., Thielemans, K., & Neyns, B. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.4121 · Cited by 312 · see citing works
A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA
Schuberth-Wagner, C., Ludwig, J., Bruder, A. K., Herzner, A., Zillinger, T., Goldeck, M., Schmidt, T., Schmid-Burgk, J. L., Kerber, R., Wolter, S., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.015 · Cited by 311 · see citing works
An Update on Self-Amplifying mRNA Vaccine Development
Blakney, A. K., Ip, S., & Geall, A. J. (2021) · Vaccines · doi:10.3390/vaccines9020097 · Cited by 288 · see citing works
Alphavirus RNA synthesis and non-structural protein functions
Rupp, J. C., Sokoloski, K. J., Gebhart, N. N., & Hardy, R. W. (2015) · Journal of General Virology · doi:10.1099/jgv.0.000249 · Cited by 285 · see citing works
Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin
Karikó, K., Muramatsu, H., Keller, J. M., & Weissman, D. (2012) · Molecular Therapy · doi:10.1038/mt.2012.7 · Cited by 282 · see citing works
Short poly(A) tails are a conserved feature of highly expressed genes
Lima, S. A., Chipman, L. B., Nicholson, A. L., Chen, Y.-H., Yee, B. A., Yeo, G. W.-M., Coller, J., & Pasquinelli, A. E. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3499 · Cited by 282 · see citing works
Nucleic acid agonists for Toll‐like receptor 7 are defined by the presence of uridine ribonucleotides
Diebold, S. S., Massacrier, C., Akira, S., Paturel, C., Morel, Y., & Sousa, C. R. E. (2006) · European Journal of Immunology · doi:10.1002/eji.200636617 · Cited by 281 · see citing works
The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms
Davies, M. V., Chang, H. W., Jacobs, B. L., & Kaufman, R. J. (1993) · Journal of Virology · doi:10.1128/jvi.67.3.1688-1692.1993 · Cited by 274 · see citing works
The Vaccinia Virus Soluble Alpha/Beta Interferon (IFN) Receptor Binds to the Cell Surface and Protects Cells from the Antiviral Effects of IFN
Alcamı́, A., Symons, J. A., & Smith, G. L. (2000) · Journal of Virology · doi:10.1128/jvi.74.23.11230-11239.2000 · Cited by 274 · see citing works
Control of poly(A) tail length
Eckmann, C. R., Rammelt, C., & Wahle, E. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.56 · Cited by 272 · see citing works
IFN‐α/β enhances BCR‐dependent B cell responses
Braun, D., Caramalho, Í., & Demengeot, J. (2002) · International Immunology · doi:10.1093/intimm/14.4.411 · Cited by 269 · see citing works
Processivity in early stages of transcription by T7 RNA polymerase
Martin, C. T., Muller, D. K., & Coleman, J. E. (1988) · Biochemistry · doi:10.1021/bi00411a012 · Cited by 264 · see citing works
Uridine Depletion and Chemical Modification Increase Cas9 mRNA Activity and Reduce Immunogenicity without HPLC Purification
Vaidyanathan, S., Azizian, K. T., Haque, A. K. M. A., Henderson, J. M., Hendel, A., Shore, S., Antony, J. S., Hogrefe, R. I., Kormann, M. S. D., Porteus, M. H., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.06.010 · Cited by 262 · see citing works
Results 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 · see citing works
Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1
de Weerd, N. A., Vivian, J. P., Nguyen, T. K., Mangan, N. E., Gould, J. A., Braniff, S.-J., Zaker-Tabrizi, L., Fung, K. Y., Forster, S. C., Beddoe, T., et al. (2013) · Nature Immunology · doi:10.1038/ni.2667 · Cited by 260 · see citing works
Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling
Zhang, H., You, X., Wang, X., Cui, L., Wang, Z., Xu, F., Li, M., Yang, Z., Liu, J., Huang, P., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2005191118 · Cited by 251 · see citing works
The Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon at the Level of the MAVS Adaptor Protein
Varga, Z. T., Ramos, I., Hai, R., Schmolke, M., García‐Sastre, A., Fernández-Sesma, A., & Palese, P. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002067 · Cited by 246 · see citing works
Small molecule ISRIB suppresses the integrated stress response within a defined window of activation
Rabouw, H. H., Langereis, M. A., Anand, A. A., Visser, L. J., de Groot, R. J., Walter, P., & van Kuppeveld, F. J. M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815767116 · Cited by 242 · see citing works
The molecular basis for differential type I interferon signaling
Schreiber, G. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.774562 · Cited by 240 · see citing works
Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus
Honke, N., Shaabani, N., Cadeddu, G., Sorg, U. R., Zhang, D., Trilling, M., Klingel, K., Sauter, M., Kandolf, R., Gailus, N., et al. (2011) · Nature Immunology · doi:10.1038/ni.2169 · Cited by 234 · see citing works
PKR Stimulates NF-κB Irrespective of Its Kinase Function by Interacting with the IκB Kinase Complex
Bonnet, M., Weil, R., Dam, E., Hovanessian, A. G., & MEURS, E. F. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.13.4532-4542.2000 · Cited by 234 · see citing works
Mechanism of action of mRNA-based vaccines
Iavarone, C., O’hagan, D. T., Yu, D., Delahaye, N. F., & Ulmer, J. B. (2017) · Expert Review of Vaccines · doi:10.1080/14760584.2017.1355245 · Cited by 234 · see citing works
RNA Interference-Induced Innate Immunity, Off-Target Effect, or Immune Adjuvant?
Meng, Z., & Lu, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00331 · Cited by 226 · see citing works
ADAR1: “Editor-in-Chief” of Cytoplasmic Innate Immunity
Lamers, M. M., van den Hoogen, B. G., & Haagmans, B. L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01763 · Cited by 224 · 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
A novel, disruptive vaccination technology: Self-adjuvanted RNActive <sup>®</sup> vaccines
Kallen, K.-J., Heidenreich, R., Schnee, M., Petsch, B., Schlake, T., Thess, A., Baumhof, P., Scheel, B., Koch, S. D., & Fotin-Mleczek, M. (2013) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.25181 · Cited by 223 · see citing works
Reprogramming human fibroblasts to pluripotency using modified mRNA
Mandal, P., & Rossi, D. J. (2013) · Nature Protocols · doi:10.1038/nprot.2013.019 · Cited by 219 · see citing works
An origin of the immunogenicity of in vitro transcribed RNA
Mu, X., Greenwald, E., Ahmad, S., & Hur, S. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky177 · Cited by 218 · see citing works
The vaccinia virus K3L gene product potentiates translation by inhibiting double-stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of eukaryotic initiation factor 2
Davies, M. V., Elroy‐Stein, O., Jagus, R., Moss, B., & Kaufman, R. J. (1992) · Journal of Virology · doi:10.1128/jvi.66.4.1943-1950.1992 · Cited by 214 · see citing works
A trans-amplifying RNA vaccine strategy for induction of potent protective immunity
Beissert, T., Perkovic, M., Vogel, A., Erbar, S., Walzer, K. C., Hempel, T., Brill, S., Haefner, E., Becker, R., Türeci, Ö., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.09.009 · Cited by 212 · see citing works
Naturally occurring modified ribonucleosides
McCown, P. J., Ruszkowska, A., Kunkler, C. N., Breger, K., Hulewicz, J. P., Wang, M. C., Springer, N. A., & Brown, J. A. (2020) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1595 · Cited by 210 · see citing works
Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design
Pepini, T., Pulichino, A.-M., Carsillo, T., Carlson, A. L., Sari-Sarraf, F., Ramsauer, K., Debasitis, J. C., Maruggi, G., Otten, G. R., Geall, A. J., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601877 · Cited by 208 · see citing works
Self-coded 3′-Extension of Run-off Transcripts Produces Aberrant Products during in Vitro Transcription with T7 RNA Polymerase
Triana‐Alonso, F. J., Dabrowski, M., Wadzack, J., & Nierhaus, K. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.11.6298 · Cited by 207 · see citing works
Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent
Probst, 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 · see citing works
In Vitro Transcription of Long RNA Containing Modified Nucleosides
Pardi, N., Muramatsu, H., Weissman, D., & Karikó, K. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-260-5_2 · Cited by 204 · see citing works
A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients
Wilgenhof, S., Nuffel, A. M. T. V., Benteyn, D., Corthals, J., Aerts, C., Heirman, C., Riet, I. V., Bonehill, A., Thielemans, K., & Neyns, B. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt245 · Cited by 204 · see citing works
A periodic pattern of mRNA secondary structure created by the genetic code
Shabalina, S. A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl287 · Cited by 202 · see citing works
Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo
Kauffman, K. J., Mir, F. F., Jhunjhunwala, S., Kaczmarek, J. C., Hurtado, J. E., Yang, J. H., Webber, M. J., Kowalski, P. S., Heartlein, M. W., DeRosa, F., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.09.006 · Cited by 191 · see citing works
Functions of the influenza A virus NS1 protein in antiviral defense
Krug, R. M. (2015) · Current Opinion in Virology · doi:10.1016/j.coviro.2015.01.007 · Cited by 188 · see citing works
RNA: The new revolution in nucleic acid vaccines
Geall, A. J., Mandl, C. W., & Ulmer, J. B. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.05.001 · Cited by 187 · see citing works
Selection of RNA Replicons Capable of Persistent Noncytopathic Replication in Mammalian Cells
Frolov, I. V., Agapov, E. V., Hoffman, T. A., Prágai, B. M., Lippa, M., Schlesinger, S., & Rice, C. M. (1999) · Journal of Virology · doi:10.1128/jvi.73.5.3854-3865.1999 · Cited by 186 · see citing works
Clinical and immunological effects of mRNA vaccines in malignant diseases
Heine, A., Juranek, S., & Brossart, P. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01339-1 · Cited by 185 · see citing works
Self-Amplifying mRNA Vaccines
Brito, L. A., Kommareddy, S., Maione, D., Uematsu, Y., Giovani, C., Scorza, F. B., Otten, G. R., Yu, D. L., Mandl, C. W., Mason, P. W., et al. (2014) · Advances in genetics · doi:10.1016/bs.adgen.2014.10.005 · Cited by 182 · see citing works
3′ end additions by T7 RNA polymerase are RNA self-templated, distributive and diverse in character—RNA-Seq analyses
Gholamalipour, Y., Mudiyanselage, A. K., & Martin, C. T. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky796 · Cited by 182 · see citing works
mRNA-based dendritic cell vaccines
Benteyn, D., Heirman, C., Bonehill, A., Thielemans, K., & Breckpot, K. (2014) · Expert Review of Vaccines · doi:10.1586/14760584.2014.957684 · Cited by 181 · see citing works
Nucleic acid vaccines: prospects for non-viral delivery of mRNA vaccines
Deering, R. P., Kommareddy, S., Ulmer, J. B., Brito, L. A., & Geall, A. J. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.901308 · Cited by 177 · see citing works
The Interferon System and Vaccinia Virus Evasion Mechanisms
Perdiguero, B., & Estéban, M. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0073 · Cited by 173 · see citing works
TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma
Keersmaecker, B. D., Claerhout, S., Carrasco, J., Bar, I., Corthals, J., Wilgenhof, S., Neyns, B., & Thielemans, K. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000329 · Cited by 168 · see citing works
mRNA transfection of dendritic cells: Synergistic effect of ARCA mRNA capping with Poly(A) chains in cis and in trans for a high protein expression level
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 · see citing works
Alphavirus polymerase and RNA replication
Pietilä, M. K., Hellström, K., & Ahola, T. (2017) · Virus Research · doi:10.1016/j.virusres.2017.01.007 · Cited by 163 · see citing works
Alphavirus Infection: Host Cell Shut-Off and Inhibition of Antiviral Responses
Fros, J. J., & Pijlman, G. P. (2016) · Viruses · doi:10.3390/v8060166 · Cited by 158 · see citing works
A sharp T-cell antigen receptor signaling threshold for T-cell proliferation
Au‐Yeung, B. B., Zikherman, J., Mueller, J. L., Ashouri, J. F., Matloubian, M., Cheng, D. A., Chen, Y., Shokat, K. M., & Weiss, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413726111 · Cited by 156 · see citing works
A Single N66S Mutation in the PB1-F2 Protein of Influenza A Virus Increases Virulence by Inhibiting the Early Interferon Response In Vivo
Conenello, G. M., Tisoncik-Go, J., Rosenzweig, E., Varga, Z. T., Palese, P., & Katze, M. G. (2010) · Journal of Virology · doi:10.1128/jvi.01987-10 · Cited by 155 · see citing works
Determinants and implications of mRNA poly(A) tail size – Does this protein make my tail look big?
Jalkanen, A. L., Coleman, S. J., & Wilusz, J. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.05.018 · Cited by 154 · see citing works
Feeder-Free Derivation of Human Induced Pluripotent Stem Cells with Messenger RNA
Warren, L., Ni, Y., Wang, J., & Guo, X. (2012) · Scientific Reports · doi:10.1038/srep00657 · Cited by 154 · see citing works
Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans
Cagigi, A., & Loré, K. (2021) · Vaccines · doi:10.3390/vaccines9010061 · Cited by 153 · see citing works
Messenger RNA-based vaccines
Pascolo, S. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.8.1285 · Cited by 152 · see citing works
B‐cell activation by membrane‐bound antigens is facilitated by the interaction of VLA‐4 with VCAM‐1
Carrasco, Y. R., & Batista, F. D. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600944 · Cited by 150 · see citing works
Noncytopathic Replication of Venezuelan Equine Encephalitis Virus and Eastern Equine Encephalitis Virus Replicons in Mammalian Cells
Petrakova, O., Volkova, E., Gorchakov, R., Paessler, S., Kinney, R., & Frolov, I. (2005) · Journal of Virology · doi:10.1128/jvi.79.12.7597-7608.2005 · Cited by 148 · see citing works
Rapid, nondenaturing RNA purification using weak anion-exchange fast performance liquid chromatography
Easton, L. E., Shibata, Y., & Lukavsky, P. J. (2010) · RNA · doi:10.1261/rna.1862210 · Cited by 143 · see citing works
In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency
Mahiny, A. J., Dewerth, A., Mays, L. E., Alkhaled, M., Mothes, B., Malaeksefat, E., Loretz, B., Rottenberger, J., Brosch, D. M., Reautschnig, P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3241 · Cited by 139 · cited 1× · see citing works
“showed that m5C/s2U-modified mRNA encoding a zinc finger nuclease (ZFN) induced a more robust protein expression in mouse lungs than unmodified mRNA and corrected SP-B deficiency in mice [96].”
Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions
Henrickson, S. E., Perro, M., Loughhead, S. M., Senman, B. C., Stutte, S., Quigley, M. M., Alexe, G., Iannacone, M., Flynn, M. P., Omid, S., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.034 · Cited by 138 · see citing works
Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner
Nallagatla, S. R., & Bevilacqua, P. C. (2008) · RNA · doi:10.1261/rna.1007408 · Cited by 137 · see citing works
Activation of NF-κB by the dsRNA-dependent protein kinase, PKR involves the IκB kinase complex
Gil, J., Alcamı́, J., & Estéban, M. (2000) · Oncogene · doi:10.1038/sj.onc.1203448 · Cited by 137 · see citing works
Synthesis of low immunogenicity RNA with high-temperature in vitro transcription
Wu, M. Z., Asahara, H., Tzertzinis, G., & Roy, B. (2020) · RNA · doi:10.1261/rna.073858.119 · Cited by 135 · see citing works
Challenges and advances towards the rational design of mRNA vaccines
Pollard, C., Koker, S. D., Saelens, X., Vanham, G. L., & Grooten, J. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.09.002 · Cited by 134 · see citing works
Purification of mRNA Encoding Chimeric Antigen Receptor Is Critical for Generation of a Robust T-Cell Response
Foster, J., Choudhari, N., Perazzelli, J., Storm, J., Hofmann, T. J., Jain, P., Storm, P. B., Pardi, N., Weissman, D., Waanders, A. J., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.145 · Cited by 133 · see citing works
Co-delivery of nucleoside-modified mRNA and TLR agonists for cancer immunotherapy: restoring the immunogenicity of immunosilent mRNA
Verbeke, R., Lentacker, I., Wayteck, L., Breckpot, K., Van Bockstal, M., Descamps, B., Vanhove, C., De Smedt, S. C., & Dewitte, H. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.041 · Cited by 132 · see citing works
Self-citation
Inhibition of the OAS/RNase L pathway by viruses
Drappier, M., & Michiels, T. (2015) · Current Opinion in Virology · doi:10.1016/j.coviro.2015.07.002 · Cited by 129 · see citing works
Codon Optimization in the Production of Recombinant Biotherapeutics: Potential Risks and Considerations
Mauro, V. P. (2018) · BioDrugs · doi:10.1007/s40259-018-0261-x · Cited by 126 · see citing works
Type I interferons interfere with the capacity of mRNA lipoplex vaccines to elicit cytolytic T cell responses
De Beuckelaer, A., Pollard, C., Van Lint, S., Roose, K., Van Hoecke, L., Naessens, T., Udhayakumar, V. K., Smet, M., Sanders, N., Lienenklaus, S., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.161 · Cited by 122 · see citing works
Self-citation
Half-lives of beta and gamma globin messenger RNAs and of protein synthetic capacity in cultured human reticulocytes
Ross, J., & Sullivan, T. (1985) · Blood · doi:10.1182/blood.v66.5.1149.1149 · Cited by 121 · see citing works
Replicon Vectors Derived from Sindbis Virus and Semliki Forest Virus That Establish Persistent Replication in Host Cells
Perri, S., Driver, D. A., Gardner, J. P., Sherrill, S., Belli, B., Dubensky, T. W., & Polo, J. M. (2000) · Journal of Virology · doi:10.1128/jvi.74.20.9802-9807.2000 · Cited by 121 · see citing works
Particle-mediated intravenous delivery of antigen mRNA results in strong antigen-specific T-cell responses despite the induction of type I interferon
Broos, K., Van der Jeught, K., Puttemans, J., Goyvaerts, C., Heirman, C., Dewitte, H., Verbeke, R., Lentacker, I., Thielemans, K., & Breckpot, K. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2016.38 · Cited by 121 · see citing works
Self-citation
mRNA therapeutics deliver a hopeful message
Zhong, Z., Cafferty, S. M., Combes, F., Huysmans, H., Temmerman, J. D., Gitsels, A., Vanrompay, D. C. G., Catani, J. P., & Sanders, N. N. (2018) · Nano Today · doi:10.1016/j.nantod.2018.10.005 · Cited by 120 · see citing works
Self-citation
Fine-Tuning of Type I Interferon Response by STAT3
Tsai, M.-H., Pai, L., & Lee, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01448 · Cited by 119 · see citing works
Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level IL-12 Secretion by Dendritic Cells
Koski, G. K., Karikó, K., Xu, S., Weissman, D., Cohen, P. A., & Czerniecki, B. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.3989 · Cited by 116 · see citing works
Identification of Mutations in a Sindbis Virus Variant Able to Establish Persistent Infection in BHK Cells: The Importance of a Mutation in the nsP2 Gene
Dryga, S. A., DRYGA, O. A., & Schlesinger, S. (1997) · Virology · doi:10.1006/viro.1996.8364 · Cited by 116 · see citing works
Regulation of α-Globin mRNA Stability
Waggoner, S. A., & Liebhaber, S. A. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322800409 · Cited by 114 · see citing works
mRNA-encoded, constitutively active STINGV155M is a potent genetic adjuvant of antigen-specific CD8+ T cell response
Tse, S., McKinney, K. M., Walker, W., Nguyen, M., Iacovelli, J., Small, C. G., Hopson, K., Zaks, T. Z., & Huang, E. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.03.002 · Cited by 113 · see citing works
Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
Devoldere, J., Dewitte, H., De Smedt, S. C., & Remaut, K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2015.07.009 · Cited by 112 · see citing works
Self-citation
Synthetic mRNA capping
Muttach, F., Muthmann, N., & Rentmeister, A. (2017) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.13.274 · Cited by 112 · see citing works
mRNA: Fulfilling the Promise of Gene Therapy
Weissman, D., & Karikó, K. (2015) · Molecular Therapy · doi:10.1038/mt.2015.138 · Cited by 111 · see citing works
Type I Interferons Modulate CD8 + T Cell Immunity to mRNA Vaccines
Beuckelaer, A. D., Grooten, J., & Koker, S. D. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.01.006 · Cited by 109 · see citing works
Rapid purification of RNAs using fast performance liquid chromatography (FPLC)
Kim, I., McKenna, S. A., Puglisi, E. V., & Puglisi, J. D. (2006) · RNA · doi:10.1261/rna.342607 · Cited by 106 · see citing works
Viral load Reduction in SHIV-Positive Nonhuman Primates via Long-Acting Subcutaneous Tenofovir Alafenamide Fumarate Release from a Nanofluidic Implant
Pons-Faudoa, F. P., Trani, N. D., Sizovs, A., Shelton, K. A., Momin, Z. K., Bushman, L. R., Xu, J., Lewis, D. E., Demaria, S., Hawkins, T., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12100981 · Cited by 105 · see citing works
Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA
Blakney, A. K., McKay, P. F., Bouton, C. R., Hu, K., Samnuan, K., & Shattock, R. J. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.011 · Cited by 105 · see citing works
ADARs: Viruses and Innate Immunity
Samuel, C. E. (2011) · Current topics in microbiology and immunology · doi:10.1007/82_2011_148 · Cited by 103 · see citing works
Influenza A Virus Protein PB1-F2 Exacerbates IFN-β Expression of Human Respiratory Epithelial Cells
Goffic, R. L., Bouguyon, E., Chevalier, C., Vidić, J., da Costa, B. R., Leymarie, O., Bourdieu, C., Decamps, L., Dhorne‐Pollet, S., & Delmas, B. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903952 · Cited by 103 · see citing works
Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection
Leal, L., Guardo, A. C., Morón‐López, S., Salgado, M., Mothe, B., Heirman, C., Pannus, P., Vanham, G., van den Ham, H., Gruters, R. A., et al. (2018) · AIDS · doi:10.1097/qad.0000000000002026 · Cited by 100 · see citing works
RNA Recognition via TLR7 and TLR8
Hornung, V., Barchet, W., Schlee, M., & Hartmann, G. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-72167-3_4 · Cited by 99 · see citing works
Influenza A virus-encoded NS1 virulence factor protein inhibits innate immune response by targeting IKK
Gao, S., Song, L., Li, J., Zhang, Z., Peng, H., Jiang, W., Wang, Q., Kang, T., Chen, S., & Huang, W. (2012) · Cellular Microbiology · doi:10.1111/cmi.12005 · Cited by 99 · see citing works
Purification and characterization of transcribed RNAs using gel filtration chromatography
McKenna, S. A., Kim, I., Puglisi, E. V., Lindhout, D. A., Aitken, C. E., Marshall, R. A., & Puglisi, J. D. (2007) · Nature Protocols · doi:10.1038/nprot.2007.480 · Cited by 98 · see citing works
Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses
Eigenbrod, T., & Dalpke, A. H. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500530 · Cited by 96 · see citing works
Self-Amplifying RNA Viruses as RNA Vaccines
Lundstrom, K. H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145130 · Cited by 96 · see citing works
pEVL: A Linear Plasmid for Generating mRNA IVT Templates With Extended Encoded Poly(A) Sequences
Grier, A. E., Burleigh, S., Sahni, J., Clough, C. A., Cardot, V., Choe, D. C., Krutein, M. C., Rawlings, D. J., Jensen, M. C., Scharenberg, A. M., et al. (2016) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2016.21 · Cited by 95 · see citing works
Innate Immune Suppression Enables Frequent Transfection with RNA Encoding Reprogramming Proteins
Angel, M., & Yanik, M. F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011756 · Cited by 91 · see citing works
The influenza virus PB1-F2 protein has interferon antagonistic activity
Dudek, S. E., Wixler, L., Nordhoff, C., Nordmann, A., Anhlan, D., Wixler, V., & Ludwig, S. (2011) · Biological Chemistry · doi:10.1515/bc.2011.174 · Cited by 89 · see citing works
Overexpression of urokinase receptor in mammalian cells following administration of the in vitro transcribed encoding mRNA
Karikó, K., Kuo, A., & Barnathan, E. S. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300930 · Cited by 89 · see citing works
Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes
Duic, I., Tadakuma, H., Harada, Y., Yamaue, R., Deguchi, K., Suzuki, Y., Yoshimura, S. H., Kato, H., Takeyasu, K., & Fujita, T. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa935 · Cited by 86 · see citing works
Replication of RNA by the DNA-dependent RNA polymerase of phage T7
Konarska, M. M., & Sharp, P. A. (1989) · Cell · doi:10.1016/0092-8674(89)90917-3 · Cited by 85 · see citing works
A Modified mRNA Vaccine Targeting Immunodominant NS Epitopes Protects Against Dengue Virus Infection in HLA Class I Transgenic Mice
Roth, C., Cantaert, T., Colas, C., Prot, M., Casadémont, I., Levillayer, L., Thalmensi, J., Langlade‐Demoyen, P., Gerke, C., Bahl, K., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01424 · Cited by 84 · see citing works
Broadening the Message: A Nanovaccine Co-loaded with Messenger RNA and α-GalCer Induces Antitumor Immunity through Conventional and Natural Killer T Cells
Verbeke, R., Lentacker, I., Breckpot, K., Janssens, J., Calenbergh, S. V., Smedt, S. C. D., & Dewitte, H. (2019) · ACS Nano · doi:10.1021/acsnano.8b07660 · Cited by 82 · see citing works
Self-citation
The Activation Mechanism of 2′-5′-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity
Lohoefener, J., Steinke, N., Kay-Fedorov, P. C., Baruch, P., Никулин, А. Д., Tishchenko, S., Manstein, D. J., & Fedorov, R. (2015) · Structure · doi:10.1016/j.str.2015.03.012 · Cited by 81 · see citing works
Improvement of In Vivo Expression of Genes Delivered by Self-Amplifying RNA Using Vaccinia Virus Immune Evasion Proteins
Beißert, T., Koste, L., Perković, M., Walzer, K. C., Erbar, S., Selmi, A., Diken, M., Kreiter, S., Türeci, Ö., & Şahin, U. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.121 · Cited by 81 · see citing works
Sustained Vaccination Coverage during the Coronavirus Disease 2019 Epidemic in the Republic of Korea
Yu, J. H., Jeong, H. J., Kim, S. J., Lee, J. Y., Choe, Y. J., Choi, E. H., & Cho, E. H. (2020) · Vaccines · doi:10.3390/vaccines9010002 · Cited by 81 · see citing works
Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines
Alfagih, I. M., Aldosari, B. N., AlQuadeib, B. T., Almurshedi, A. S., & Alfagih, M. M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics13010045 · Cited by 79 · see citing works
Therapeutic Cancer Vaccination with Ex Vivo RNA-Transfected Dendritic Cells—An Update
Dörrie, J., Schaft, N., Schuler, G., & Schuler‐Thurner, B. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020092 · Cited by 77 · see citing works
The 3′ Untranslated Region of Sindbis Virus Represses Deadenylation of Viral Transcripts in Mosquito and Mammalian Cells
Garneau, N. L., Sokoloski, K. J., Opyrchal, M., Neff, C. P., Wilusz, C. J., & Wilusz, J. (2007) · Journal of Virology · doi:10.1128/jvi.01205-07 · Cited by 76 · see citing works
Efficient Reprogramming of Human Fibroblasts and Blood-Derived Endothelial Progenitor Cells Using Nonmodified RNA for Reprogramming and Immune Evasion
Poleganov, M. A., Eminli, S., Beißert, T., Herz, S., Moon, J.-I., Goldmann, J. E., Beyer, A., Heck, R., Burkhart, I., Roldán, D. B., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.045 · Cited by 76 · see citing works
LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses
Sanchez-David, R. Y., Combredet, C., Najburg, V., Millot, G. A., Beauclair, G., Schwikowski, B., Léger, T., Camadro, J., Jacob, Y., Bellalou, J., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aar3993 · Cited by 75 · see citing works
mRNA as a Versatile Tool for Exogenous Protein Expression
Kuhn, A. N., Beißert, T., Simon, P., Vallazza, B., Buck, J., Davies, B. P., Türeci, Ö., & Şahin, U. (2012) · Current Gene Therapy · doi:10.2174/156652312802762536 · Cited by 73 · see citing works
mRNA-based therapeutics–Advances and perspectives
Sergeeva, O. V., Koteliansky, V., & Zatsepin, T. S. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916070075 · Cited by 72 · see citing works
Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment
Dewitte, H., Verbeke, R., Breckpot, K., Smedt, S. C. D., & Lentacker, I. (2014) · Nano Today · doi:10.1016/j.nantod.2014.10.001 · Cited by 71 · see citing works
Self-citation
In vitro evolution of enhanced RNA replicons for immunotherapy
Li, Y., Teague, B., Zhang, Y., Su, Z., Porter, E., Dobosh, B., Wagner, T., Irvine, D. J., & Weiss, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-43422-0 · Cited by 71 · see citing works
Messenger RNA (mRNA) nanoparticle tumour vaccination
Phua, K. K. L., Nair, S. K., & Leong, K. W. (2014) · Nanoscale · doi:10.1039/c4nr01346h · Cited by 70 · see citing works
Molecular Insights into Reprogramming-Initiation Events Mediated by the OSKM Gene Regulatory Network
Mah, N., Wang, Y., Liao, M.-C., Prigione, A., Józefczuk, J., Lichtner, B., Wolfrum, K., Haltmeier, M., Flöttmann, M., Schaefer, M. H., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024351 · Cited by 70 · see citing works
Stress Resilience of Spermatozoa and Blood Mononuclear Cells without Prion Protein
Reiten, M. R., Malachin, G., Kommisrud, E., Østby, G. C., Waterhouse, K. E., Krogenæs, A., Kuśnierczyk, A., Bjørås, M., Jalland, C. M. O., Nekså, L. H., et al. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00001 · Cited by 69 · see citing works

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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
Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications
Shi, Y., Shi, M., Wáng, Y., & You, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02002-z · Cited by 231 · see citing works
Chemically Modified Platforms for Better RNA Therapeutics
Shi, Y., Zhen, X., Zhang, Y., Li, Y., Koo, S., Saiding, Q., Kong, N., Liu, G., Chen, W., & Tao, W. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00611 · Cited by 184 · see citing works
Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines
Kim, B., Hosn, R. R., Remba, T. K., Yun, D. S., Li, N., Abraham, W. D., Melo, M. B., Cortés, M., Li, B., Zhang, Y., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.022 · Cited by 154 · see citing works
mRNA in the Context of Protein Replacement Therapy
Vavilis, T., Stamoula, Ε., Ainatzoglou, A., Sachinidis, A., Lamprinou, M., Dardalas, I., & Vizirianakis, I. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010166 · Cited by 143 · see citing works
Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity
Zhang, H., Vandesompele, J., Braeckmans, K., Smedt, S. C. D., & Remaut, K. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00194f · Cited by 140 · see citing works
Self-citation
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
Quality by Design for enabling RNA platform production processes
Daniel, S., Kis, Z., Kontoravdi, C., & Shah, N. (2022) · Trends in biotechnology · doi:10.1016/j.tibtech.2022.03.012 · Cited by 128 · see citing works
Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases
Yang, J., Tseng, J., Yu, G., Luo, Y., Huang, C. F., Hong, Y., & Chuang, T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020423 · Cited by 127 · see citing works
The advent of clinical self-amplifying RNA vaccines
Casmil, I. C., Jin, J., Won, E.-J., Huang, C., Liao, S., Cha‐Molstad, H., & Blakney, A. K. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.060 · Cited by 105 · see citing works
Frameworks for transformational breakthroughs in RNA-based medicines
Androsavich, J. R. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00943-2 · Cited by 93 · see citing works
RNA chemistry and therapeutics
Wang, S., Weissman, D., & Dong, Y. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01237-x · Cited by 98 · see citing works
Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications
Chan, A., & Tsourkas, A. (2023) · BME Frontiers · doi:10.34133/bmef.0035 · Cited by 90 · see citing works
Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency
McGee, J. E., Kirsch, J. R., Kenney, D., Cerbo, F., Chavez, E. C., Shih, T.-Y., Douam, F., Wong, W. W., & Grinstaff, M. W. (2025) · Nature Biotechnology · doi:10.1038/s41587-024-02306-z · Cited by 87 · see citing works
“Preclinical and clinical data confirm that the early and intense IFN response inhibits antigen expression and induces inflammation 5,13,14,35 .”
BackgroundInfluential
mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases
Le, T., Sun, C., Chang, J., Zhang, G., & Yin, X. (2022) · Viruses · doi:10.3390/v14020401 · Cited by 93 · see citing works
Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development
Schmidt, C., & Schnierle, B. S. (2023) · Pathogens · doi:10.3390/pathogens12010138 · Cited by 78 · see citing works
Self-Amplifying RNA Approach for Protein Replacement Therapy
Papukashvili, D., Rcheulishvili, N., Liu, C., Ji, Y., He, Y., & Wang, P. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112884 · Cited by 76 · see citing works
mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles
Ouranidis, A., Vavilis, T., Mandala, E., Davidopoulou, C., Stamoula, Ε., Markopoulou, C. K., Karagianni, A., & Kachrimanis, K. (2021) · Biomedicines · doi:10.3390/biomedicines10010050 · Cited by 72 · see citing works
Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
Vallet, T., & Vignuzzi, M. (2025) · Viruses · doi:10.3390/v17040566 · Cited by 73 · see citing works
A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs
Bogaert, B., Sauvage, F., Guagliardo, R., Muntean, C., Nguyen, V. P., Pottie, E., Wels, M., Minnaert, A., Rycke, R. M. D., Yang, Q., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.08.009 · Cited by 68 · see citing works
Self-citation
mRNA: A promising platform for cancer immunotherapy
Kong, B., Kim, Y., Kim, E. H., Suk, J. S., & Yang, Y. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114993 · Cited by 67 · see citing works
Delivery of mRNA for regulating functions of immune cells
Shi, J. Y., Huang, M., Lu, Z.-D., Du, X., Shen, S., Xu, C., & Wang, J. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.033 · Cited by 62 · see citing works
Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications
Yan, Y., Liu, S., Wen, J., He, Y., Duan, C., Nabavi, N., Ashrafizadeh, M., Sethi, G., Liu, L., & Ma, R. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02463-y · Cited by 68 · see citing works
The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines
Wei, J., & Hui, A.-M. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102405 · Cited by 57 · see citing works
Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy
Wang, Y., Zhang, R., Tang, L., & Li, Y. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030512 · Cited by 57 · see citing works
Advances of mRNA vaccine in tumor: a maze of opportunities and challenges
Yuan, Y., Gao, F., Chang, Y., Zhao, Q., & He, X. (2023) · Biomarker Research · doi:10.1186/s40364-023-00449-w · Cited by 58 · see citing works
Self-amplifying mRNA vaccines: Mode of action, design, development and optimization
Pourseif, M. M., Masoudi‐Sobhanzadeh, Y., Azari, E., Parvizpour, S., Barar, J., Ansari, R. A., & Omidi, Y. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103341 · Cited by 54 · see citing works
BiTE‐Secreting CAR‐γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors
Huang, S., Pan, C., Lin, Y., Chen, M., Chen, Y., Jan, C., Wu, C., Lin, F., Wang, S. Y., Lin, C., et al. (2023) · Advanced Science · doi:10.1002/advs.202206856 · Cited by 55 · see citing works
Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines
Tregoning, J. S., Stirling, D. C., Wang, Z., Flight, K. E., Brown, J. C., Blakney, A. K., McKay, P. F., Cunliffe, R. F., Murugaiah, V., Fox, C. B., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.11.024 · Cited by 57 · see citing works
In situ engineering of mRNA-CAR T cells using spleen-targeted ionizable lipid nanoparticles to eliminate cancer cells
Li, Y., Tian, Y., Li, C., Fang, W., Li, X., Jing, Z., Yang, Z., Zhang, X., Huang, Y., Gong, J., et al. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102518 · Cited by 54 · see citing works
A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation
Kimura, T., Leal, J. M., Simpson, A., Warner, N. L., Berube, B. J., Archer, J. F., Park, S., Kurtz, R., Hinkley, T., Nicholes, K., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.06.017 · Cited by 52 · see citing works
Modulating intracellular pathways to improve non-viral delivery of RNA therapeutics
de Vyver, T. V., Smedt, S. C. D., & Raemdonck, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114041 · Cited by 51 · see citing works
Self-citation
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
Cellular Trafficking of Nanotechnology‐Mediated mRNA Delivery
Huang, P., Deng, H., Wang, C., Zhou, Y., & Chen, X. S. (2023) · Advanced Materials · doi:10.1002/adma.202307822 · Cited by 49 · see citing works
Advancements and challenges in mRNA and ribonucleoprotein-based therapies: From delivery systems to clinical applications
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Advances and applications of RNA vaccines in tumor treatment
Yang, R., & Cui, J. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02141-5 · Cited by 48 · see citing works
GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults
Palmer, C. D., Scallan, C. D., Kraemer Tardif, L. D., Kachura, M. A., Rappaport, A. R., Koralek, D. O., Uriel, A., Gitlin, L., Klein, J., Davis, M. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39053-9 · Cited by 42 · see citing works
Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity
Bathula, N. V., Friesen, J. J., Casmil, I. C., Wayne, C. J., Liao, S., Soriano, S. K. V., Ho, C.-H., Strumpel, A., & Blakney, A. K. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.07.078 · Cited by 42 · see citing works
Synthetic mRNA – emerging new class of drug for tissue regeneration
Balmayor, E. R. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.10.015 · Cited by 36 · see citing works
Effect of in vitro transcription conditions on yield of high quality messenger and self-amplifying RNA
Popova, P. G., Lagace, M. A., Tang, G., & Blakney, A. K. (2024) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2024.114247 · Cited by 33 · see citing works
SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells
Stevenson, E. M., Terry, S. N., Copertino, D. C., Leyre, L., Danesh, A., Weiler, J., Ward, A. R., Khadka, P., McNeil, E. P., Bernard, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32376-z · Cited by 33 · see citing works
Path towards mRNA delivery for cancer immunotherapy from bench to bedside
Chen, W., Zhu, Y., He, J., & Sun, X. (2023) · Theranostics · doi:10.7150/thno.89247 · Cited by 31 · see citing works
Amplification of Protein Expression by Self-Amplifying mRNA Delivered in Lipid Nanoparticles Containing a β-Aminoester Ionizable Lipid Correlates with Reduced Innate Immune Activation
Lombaerde, E. D., Cui, X., Chen, Y., Zhong, Z., Deckers, J., Mencarelli, G., Opsomer, L., Wang, H., Baere, J. D., Lienenklaus, S., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c09677 · Cited by 31 · see citing works
Self-citation
Engineering challenges and translational opportunities in emerging gene delivery platforms
Ma, Y., Dong, S., Wu, A., Jeong, S. D., Lee, A. S., Jiang, W., & Kim, B. Y. S. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01643-5 · Cited by 30 · see citing works
A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections
Schmidt, C., Haefner, E. S., Gerbeth, J., Beißert, T., Şahin, U., Perković, M., & Schnierle, B. S. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.04.036 · Cited by 28 · see citing works
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Feng, S., Rcheulishvili, N., Jiang, X., Zhu, P., Pan, X., Wei, M., Wang, P. G., Ji, Y., & Papukashvili, D. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.87741 · Cited by 27 · see citing works
Advancing mRNA technologies for therapies and vaccines: An African context
Kairuz, D., Samudh, N., Ely, A., Arbuthnot, P., & Bloom, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018961 · Cited by 25 · see citing works
“Post-transcriptional purification of synthetic mRNAs is necessary to remove immunogenic dsDNA templates and dsRNA by-products, aborted transcripts, excess reagents, and other chemical by-products to obtain full-length mRNA transcripts which would then be acceptable as pharmaceutical grade therapeutics and vaccines (re…”
Background
Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity
Gong, N., Kim, D., Alameh, M., El-Mayta, R. D., Han, E. L., Dwivedi, G., Palanki, R., Shi, Q., Han, X., Xue, L., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01422-8 · Cited by 27 · see citing works
Host Cell Restriction Factors Blocking Efficient Vector Transduction: Challenges in Lentiviral and Adeno-Associated Vector Based Gene Therapies
Coroadinha, A. S. (2023) · Cells · doi:10.3390/cells12050732 · Cited by 25 · see citing works
RETRACTED ARTICLE: Neoantigen vaccine nanoformulations based on Chemically synthesized minimal mRNA (CmRNA): small molecules, big impact
İmani, S., Tagit, O., & Pichon, C. (2024) · npj Vaccines · doi:10.1038/s41541-024-00807-1 · Cited by 25 · see citing works
Retracted
RNA therapies for CNS diseases
Francesco, V. D., Chua, A. J. K., Huang, D., D’souza, A. A., Yang, A., Bleier, B. S., & Amiji, M. M. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115283 · Cited by 24 · see citing works
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Nasr, S. S., Lee, S., Thiyagarajan, D., Boese, A. S., Loretz, B., & Lehr, C. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111924 · Cited by 22 · see citing works
mRNA medicine: Recent progresses in chemical modification, design, and engineering
Hou, X., Shi, J., & Xiao, Y. (2024) · Nano Research · doi:10.1007/s12274-024-6978-6 · Cited by 23 · see citing works
The clinical progress and challenges of mRNA vaccines
Yu, M., Wang, N., Zhu, J., & Lin, Y. (2023) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1894 · Cited by 22 · see citing works
A Bivalent Trans-Amplifying RNA Vaccine Candidate Induces Potent Chikungunya and Ross River Virus Specific Immune Responses
Schmidt, C., Hastert, F. D., Gerbeth, J., Beißert, T., Şahin, U., Perković, M., & Schnierle, B. S. (2022) · Vaccines · doi:10.3390/vaccines10091374 · Cited by 20 · see citing works
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Li, W., Vanluchene, H., Raes, L., Peynshaert, K., Veys, L., Hernández, S. G., Lombaerde, E. D., Geest, B. G. D., Sanders, N. N., Moons, L., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114027 · Cited by 19 · see citing works
Self-citation
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Lima, E. S., dos Santos, D., Souza, A. L., de Macedo, M. E. O., Bandeira, M. E., Silva, S. S., Fiuza, B. S. D., Rocha, V. P. C., Fonseca, L. M. D. S., Nunes, D. D. G., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16121634 · Cited by 19 · see citing works
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mRNA therapeutics for disease therapy: principles, delivery, and clinical translation
Zhou, D., Wang, K., Zhang, Y., Ma, K., Yang, X., Li, Z.-Y., Yu, S., Chen, K., & Qiao, S. (2023) · Journal of Materials Chemistry B · doi:10.1039/d2tb02782h · Cited by 17 · see citing works
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Lin, G., Tang, Y., Fu, Z., Chen, R., Liu, Y., Liu, Z., Kuang, X., Sun, J., Zhao, J., & Zhang, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.12.003 · Cited by 16 · see citing works
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Meulewaeter, S., Zhang, Y., Wadhwa, A., Fox, K., Lentacker, I., Harder, K. W., Cullis, P. R., Smedt, S. C. D., Cheng, M. H. Y., & Verbeke, R. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168385 · Cited by 13 · see citing works
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Alam, W., Tahir, M., Hussain, S., Gul, S., Hayat, M., Irshad, R. R., & Pallonetto, F. (2024) · IEEE Access · doi:10.1109/access.2024.3352823 · Cited by 13 · see citing works
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Delehedde, C., Ciganek, I., Rameix, N., Laroui, N., Gonçalves, C., Even, L., Midoux, P., & Pichon, C. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123531 · Cited by 13 · see citing works
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Peña, A. C. D., Li, N., Vaduva, M., Bwanali, L., & Tripathi, A. (2023) · The Analyst · doi:10.1039/d3an00281k · Cited by 12 · see citing works
Non-viral delivery of RNA for therapeutic T cell engineering
Berdecka, D., Smedt, S. C. D., Vos, W. H. D., & Braeckmans, K. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115215 · Cited by 14 · see citing works
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Wojcechowskyj, J. A., Jong, R. M., Mäger, I., Flach, B., Munson, P. V., Mukherjee, P. P., Mertins, B., Barcay, K. R., & Folliard, T. (2025) · npj Vaccines · doi:10.1038/s41541-025-01135-8 · Cited by 12 · see citing works
Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets
McKay, P. F., Zhou, J., Frise, R., Blakney, A. K., Bouton, C. R., Wang, Z., Hu, K., Samnuan, K., Brown, J. C., Kugathasan, R., et al. (2022) · Oxford Open Immunology · doi:10.1093/oxfimm/iqac004 · Cited by 12 · see citing works
Circular RNA therapeutics: a new class of long-acting RNA medicines for oncology, immunology, and rare diseases
Ugwu, O. P.-C., Okon, M. B., Ogenyi, F. C., Ugwu, J. N., & Ugwu, C. N. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1758902 · Cited by 10 · see citing works
The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy
Song, J., Zhang, Y., Zhou, C., Zhan, J., Cheng, X., Huang, H., Mao, S., & Zong, Z. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112037 · Cited by 10 · see citing works
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Okada, Y., Kumagai, Y., Okura, I., Otsuki, M., Ishida, N., Iwama, Y., Minamida, T., Yagi, Y., Kurosawa, T., van Boxmeer, J., et al. (2024) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(24)00565-6 · Cited by 10 · see citing works
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Chen, F., Ren, S., Huang, L., Wu, Q., Li, M., Li, S., Gao, J., Lai, Y., Cai, Z., Liu, X., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c06028 · Cited by 9 · see citing works
Development of a multi-epitope vaccine against Helicobacter pylori using a novel saRNA technology through an immunoinformatics approach
Razzak, A., Ahmed, F., & Mahmud, M. T. (2025) · Scientific Reports · doi:10.1038/s41598-025-99512-9 · Cited by 9 · see citing works
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Do, C. T. P., Prochnau, J. Y., Domínguez, A. M., Wang, P., & Rao, M. K. (2024) · Biomedicines · doi:10.3390/biomedicines12091979 · Cited by 9 · see citing works
Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer
Tang, L., Que, H., Wei, Y., Yang, T., Tong, A., & Wei, X. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01694-2 · Cited by 10 · see citing works
Cell-specific mRNA delivery via nanobody-functionalized lipid nanoparticles
Chen, L., der Weken, H. V., Zwaenepoel, O., Okkelman, I. A., Aelvoet, J., Denberghe, E. V., Gettemans, J., Dmitriev, R. I., Geest, B. G. D., Cox, E., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114365 · Cited by 8 · see citing works
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Bayraktutan, H., Kopiasz, R. J., Elsherbeny, A., Gurnani, P., & Alexander, C. (2025) · Chemical Science · doi:10.1039/d5sc05951h · Cited by 8 · see citing works
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Borbone, N., Piccialli, I., Falanga, A. P., Piccialli, V., Roviello, G. N., & Oliviero, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084359 · Cited by 8 · see citing works
Malaria vaccine approaches leveraging technologies optimized in the COVID-19 era
Kanoi, B. N., Maina, M., Likhovole, C., Kobia, F., & Gitaka, J. (2022) · Frontiers in Tropical Diseases · doi:10.3389/fitd.2022.988665 · Cited by 8 · see citing works
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Casmil, I. C., Huang, C., & Blakney, A. K. (2023) · Scientific Reports · doi:10.1038/s41598-023-46314-6 · Cited by 9 · see citing works
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Lim, T. K. Y., Ritoux, A., Paine, L. W., Ferguson, L., Abdul, T., Grundy, L. J., & Smith, E. S. J. (2025) · eLife · doi:10.7554/elife.105978.3 · Cited by 8 · see citing works
The Application of mRNA Technology for Vaccine Production—Current State of Knowledge
Paczkowska, A., Hoffmann, K., Andrzejczak, A., Pucek, W. F., Kopciuch, D., Bryl, W., Nowakowska, E., & Kus, K. (2025) · Vaccines · doi:10.3390/vaccines13040389 · Cited by 6 · see citing works
Trans amplifying mRNA vaccine expressing consensus spike elicits broad neutralization of SARS CoV 2 variants
Gontu, A., Misra, S., Chothe, S. K., Ramasamy, S., Jakka, P., Byukusenge, M., LaBella, L. C., Nair, M. S., Jayarao, B. M., Archetti, M., et al. (2025) · npj Vaccines · doi:10.1038/s41541-025-01166-1 · Cited by 6 · see citing works
Self-amplifying mRNA nanovaccine encoding GM-CSF-fused HPV16 E7 enhances immunogenicity and therapeutic efficacy against cervical cancer
Lin, G., Guo, X., Fu, Z., Liu, Z., Gu, F., Yan, H., Chen, R., Liu, Y., Kuang, X., Xu, Y., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.148933 · Cited by 5 · see citing works
Targeted suppression of type 1 interferon signaling during RNA delivery enhances vaccine-elicited immunityPreprint
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Engineered VPg saRNA achieves cap-independent, low-immunogenic and precise encoding of therapeutic proteins in vivo
Feng, Z., Chu, L., Li, Q., Zhou, J., Wu, P., Zhang, X., Pan, Y., Zou, J., Chen, Q., Xu, Z., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68364-w · Cited by 4 · see citing works
Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
Panella, R., Zanderigo, F., Morandini, F., Federico, D., Vicentini, E., Andreetta, F., Toniolo, A., & Kauppinen, S. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1125654 · Cited by 4 · see citing works
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Guterres, A., Filho, P. N. S., & Moura‐Neto, V. (2024) · Vaccines · doi:10.3390/vaccines12010061 · Cited by 4 · see citing works
Next-Generation saRNA Platforms: Systematic Screening and Engineering Enhances Superior Protein Expression and Organ-Specific Targeting for RNA TherapeuticsPreprint
Sun, Z. F., Liu, Y., Zhang, H., Ge, T., Pan, Y., Liu, Y., Wu, M., Shan, T., Zhu, G., Wu, Q., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.30.644708 · Cited by 4 · see citing works
Nanoparticle-Based mRNA Vaccine Induces Protective Neutralizing Antibodies Against Infectious Bronchitis Virus in In-Vivo Infection
Sakhrie, A., Kalluri, A., Helal, Z. H., Kumar, C. V., & Khan, M. I. (2025) · Vaccines · doi:10.3390/vaccines13060568 · Cited by 3 · see citing works
Development of mRNA Cancer Vaccines: Delivery Strategies and Immunogenicity Optimization
Ali, A. (2025) · Current Medical Science · doi:10.1007/s11596-025-00127-y · Cited by 4 · see citing works
Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy
Chen, H., Zhang, J., Huang, J., Wu, Z., Tang, L., Tian, Y., Gao, S., Huang, S., Cao, J., Chen, J., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07470-7 · Cited by 3 · see citing works
Lipid nanoparticle–based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways
Singh, N. S. S., Gataa, I. S., Saleh, L. H., Ganesan, S., Kavitha, V., Maharana, L., Sharma, R., Latipova, M., Madatova, N., Jumanazarov, D., et al. (2025) · Archives of Microbiology · doi:10.1007/s00203-025-04596-6 · Cited by 3 · see citing works
A single ultra-low dose self-amplifying RNA rabies vaccine confers rapid and complete protection in mice
Zhao, D., Chen, G., Wang, S., Suo, Y., Ye, Q., Xing, R., Yang, Y., Li, Z., XuelianWang, Zhou, R., et al. (2025) · Vaccine · doi:10.1016/j.vaccine.2025.128150 · Cited by 3 · see citing works
Formulation and administration timing of lipid derivatized JAK-inhibitor and corticosteroid modulate saRNA-LNP inflammation and expression
Bathula, N. V., Casmil, I. C., Friesen, J. J., Yuan, E., Liao, S., Maiti, B., Liou, J., Lai, M.-J., Li, S., Chen, S., et al. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114736 · Cited by 3 · see citing works
An engineered linear cap-independent mRNA vaccine with intrinsic adjuvanticity induces potent anti-tumor immunity in mice
Yu, H., Yang, Y., Lin, P., Liu, C., Wen, Y., Huang, Z., Fang, Z., Hu, Z., & St, H. (2026) · Nature Communications · doi:10.1038/s41467-026-69972-2 · Cited by 3 · see citing works
In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation
Yadav, V., Yadav, P., Mallappa, S., & Neeli, P. (2026) · Biomedicines · doi:10.3390/biomedicines14061276 · Cited by 3 · see citing works

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development
Schmidt, C., & Schnierle, B. S. (2023) · Pathogens · doi:10.3390/pathogens12010138 · Cited by 78 · 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
Self-amplifying mRNA vaccines: Mode of action, design, development and optimization
Pourseif, M. M., Masoudi‐Sobhanzadeh, Y., Azari, E., Parvizpour, S., Barar, J., Ansari, R. A., & Omidi, Y. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103341 · Cited by 54 · see citing works
Self-amplifying RNA—opportunities and challenges
Groppo, R. (2024) · Nucleic Acid Insights · doi:10.18609/nai.2024.025 · Cited by 1 · see citing works
Self-replicating RNA for mRNA vaccine development
Lundstrom, K. H. (2024) · Cell and Gene Therapy Insights · doi:10.18609/cgti.2024.074

Authors: Minnaert, A.-K., Vanluchene, H., Verbeke, R., Lentacker, I., De Smedt, S. C., Raemdonck, K., Sanders, N. N., & Remaut, K.
Affiliations: Ghent University (BE)
Corresponding author: Remaut, Katrien
ORCID: Minnaert, An-Katrien
Vanluchene, Helena
Verbeke, Rein
Lentacker, Ine
Raemdonck, Koen
Sanders, Niek N.
Remaut, Katrien
Venue: Advanced Drug Delivery Reviews
Publisher: Elsevier BV
Published: 2021-09
Volume: 176
Pages: 113900
ISSN: 0169-409X (ISSN-L)
DOI: 10.1016/j.addr.2021.113900
PMC: PMC8325057
OpenAlex: W3187029494
Cited by: 157
References: 253
Citations by year: 2026: 32 · 2025: 42 · 2024: 30 · 2023: 25 · 2022: 23 · 2021: 5
FWCI: 2.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Advanced Drug Delivery Reviews (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
Funders: European Commission (HORIZON2020, 810685)
Fonds Wetenschappelijk Onderzoek (1S28420N, 11A6320N)
Universiteit Gent
Vlaamse regering (BOF20/PDO/041, 11A6320N)
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 therapeutics, self-amplifying mRNA, innate immunity, mRNA vaccines, mRNA translation, immunotherapy, COVID-19 vaccines
MeSH terms: COVID-19, mRNA Vaccines, Animals, Gene Amplification, Humans, Immunity, Innate, Immunotherapy, RNA, Messenger, Vaccines, Synthetic

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Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics: Getting the message across

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