The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability
Open accessAbstract
In vitro-transcribed mRNAs encoding physiologically important proteins have considerable potential for therapeutic applications. However, in its present form, mRNA is unfeasible for clinical use because of its labile and immunogenic nature. Here, we investigated whether incorporation of naturally modified nucleotides into transcripts would confer enhanced biological properties to mRNA. We found that mRNAs containing pseudouridines have a higher translational capacity than unmodified mRNAs when tested in mammalian cells and lysates or administered intravenously into mice at 0.015-0.15 mg/kg doses. The delivered mRNA and the encoded protein could be detected in the spleen at 1, 4, and 24 hours after the injection, where both products were at significantly higher levels when pseudouridine-containing mRNA was administered. Even at higher doses, only the unmodified mRNA was immunogenic, inducing high serum levels of interferon-alpha (IFN-alpha). These findings indicate that nucleoside modification is an effective approach to enhance stability and translational capacity of mRNA while diminishing its immunogenicity in vivo. Improved properties conferred by pseudouridine make such mRNA a promising tool for both gene replacement and vaccination.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both of the candidates are pharmacologically optimized 15,16 , N 1 -methylpseudouridine nucleoside-modified mRNAs 17 that are administered intramuscularly in a prime-boost regimen 21”
From BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans (2021) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“which is widely believed to be critical to the recent success of mRNA vaccines1,2,10,37,38”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [38]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein.”
From Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine (2020) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Substitution of chemically modified nucleotides in messenger ribonucleic acid (mRNA) enhances stability and transfection capability, and decreases immunogenicity1–3”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This can be circumvented by the incorporation of naturally occurring nucleosides and by applying stringent purification to remove double-stranded RNA contaminants (19–21).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [20]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Karikó et al. reported that mRNA with nucleoside modifications were insensitive to ribonuclease L (RNase L) degradation, did not activate TLRs and protein kinase R, which subsequently resulted in improved translational efficiency and stability, compared to unmodified mRNA (20).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Substitution of uridine with m1Ψ in mRNA significantly improves the translation efficiency and decreases innate immunogenicity (20).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For instance, a successful approach to avoid overactivation of the innate immunity and increase translation of mRNA is the use of modified nucleosides such as methyl-pseudo uridine.29”
From Combining an optimized mRNA template with a double purification process allows strong expression of in vitro transcribed mRNA (2021) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The two uridine analogs pseudouridine (Ψ) or 1-methyl-pseudouridine (m1Ψ) are widely used for mRNA therapeutics because they can increase mRNA stability and help modulate the host immune response31,32.”
From Human 5′ UTR design and variant effect prediction from a massively parallel translation assay (2019) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In particular, we focused on ψ and m1ψ, since these substitutions for U have been widely adopted for mRNA therapeutics and vaccines due to improved in-cell translation and to better control of innate immune responses2,3,8,67 through avoidance of recognition by cellular toll-like receptors (TLR7 and TLR8)68, RIG‑I, and PKR69–71.”
From Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics (2022) · cites this paper as [69]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Replacing of uridine by pseudouridine into mRNA gives superior nonimmunogenic mRNA with increased translational capacity and biological stability (20).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Our work principally confirms that conventional unmodified mRNAs are inferior to molecules harboring specific nucleoside modifications as suggested by various recent reports,23,24,25,26,27 however, the picture changes dramatically with a sophisticated sequence-engineering.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“Although pseudouridine is primarily found in tRNA, rRNA, and small nuclear RNAs, pseudouridine-containing mRNAs were still translated and produced even more protein compared to unmodified mRNA.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“As mammalian host cells attack unmodified exogeneous RNA [12,13], all U nucleotides were replaced by N1-methylpseudouridine (Ψ) [14,15].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [12]
In the citing paper
“To avoid this, Karikó and colleagues found that adding modified nucleosides during IVT of mRNA can significantly reduce the host inflammatory response without affecting protein expression.81,159”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [159]
In the citing paper
“Studies have found that replacing original nucleosides with m6A and s2U inhibits activation of TLR3, whereas activation of TLR7 and TLR8 is blocked when using ψ, 5-methyluridine (m5U), m6A, and s2U, thereby inhibiting the innate immune responses and improving protein translation efficiency.81,159,171”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [159]
In the citing paper
“However, the incorporation of modified nucleosides into mRNA can significantly improve the biological stability and translational capacity of the mRNA while decreasing the innate immune response.36, 37, 38”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [37]
In the citing paper
“These alterations possibly lead to a blunted specific immune response.37,133, 134, 135”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [37]
In the citing paper
“Nevertheless, immune responses to IVT mRNA may also suppress antigen expression and negatively affect vaccine efficacy175,180,181.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [180]
In the citing paper
“Taken together, these findings resulted in a paradigm of the design of mRNA formulations for vaccination.One strategy is to use mRNA which is fully optimized to obtain a strong adjuvant effect, another is to work with 'modified' mRNA with high translation capacity, and thus improved antigen bio-availability [43,62].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [43]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
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
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 4,022
Self-citationSpecies-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
Self-citationLMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., et al. (2003) · Science · doi:10.1126/science.1088547 · Cited by 3,587
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C. (2004) · Science · doi:10.1126/science.1093616 · Cited by 3,444
Self-citationLutz, M. B., Kukutsch, N. A., Ogilvie, A. L. J., Rößner, S., Koch, F., Romani, N., & Schuler, G. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00204-x · Cited by 2,972
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728
Self-citation5'-Triphosphate RNA Is the Ligand for RIG-I
Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., et al. (2006) · Science · doi:10.1126/science.1132505 · Cited by 2,474
Self-citationRaper, S. E., Chirmule, N. B., Lee, F. S., Wivel, N. A., Bagg, A., Gao, G., Wilson, J. M., & Batshaw, M. L. (2003) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2003.08.016 · Cited by 1,531
Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 501–600 of 1,003
tRNA modifications tune m6A-dependent mRNA decay
Linder, B., Sharma, P., Wu, J., Birbaumer, T., Eggers, C., Murakami, S., Ott, R., Fenzl, K., Vorgerd, H., Erhard, F., et al. (2025) · Cell · doi:10.1016/j.cell.2025.04.013 · Cited by 49
Nebulisation of IVT mRNA Complexes for Intrapulmonary Administration
Johler, S. M., Rejman, J., Guan, S., & Rosenecker, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137504 · Cited by 46
Cardiovascular consequences of viral infections: from COVID to other viral diseases
Schultheiß, H., Baumeier, C., Pietsch, H., Bock, C. –., Poller, W. C., & Escher, F. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab315 · Cited by 48
Programmable RNA base editing via targeted modifications
Song, J., Zhuang, Y., & Yi, C. (2024) · Nature Chemical Biology · doi:10.1038/s41589-023-01531-y · Cited by 44
Lipid nanoparticle (LNP) mediated mRNA delivery in neurodegenerative diseases
Moosavi, S. G., Rahiman, N., Jaafari, M. R., & Arabi, L. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113641 · Cited by 54
Synthetic mRNAs for manipulating cellular phenotypes: an overview
Quabius, E. S., & Krupp, G. (2014) · New Biotechnology · doi:10.1016/j.nbt.2014.04.008 · Cited by 47
mRNA Vaccines against Flaviviruses
Wollner, C. J., & Richner, J. M. (2021) · Vaccines · doi:10.3390/vaccines9020148 · Cited by 44
Strategy of developing nucleic acid-based universal monkeypox vaccine candidates
Papukashvili, D., Rcheulishvili, N., Liu, C., Wang, X., He, Y., & Wang, P. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1050309 · Cited by 45
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
Fine-tuning of polyaspartamide derivatives with alicyclic moieties for systemic mRNA delivery
Yum, J., Kim, B. S., Ogura, S., Kamegawa, R., Naito, M., Yamasaki, Y., Kim, H. J., & Miyata, K. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.12.040 · Cited by 43
Chemically Modified mocRNAs for Highly Efficient Protein Expression in Mammalian Cells
Aditham, A. J., Shi, H., Guo, J., Zeng, H., Zhou, Y., Wade, S. D., Huang, J., Jia Liu, B., & Wang, X. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.1c00569 · Cited by 45
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 47
Nanoscale delivery platforms for RNA therapeutics: Challenges and the current state of the art
Rhym, L. H., & Anderson, D. G. (2022) · Med · doi:10.1016/j.medj.2022.02.001 · Cited by 45
Tanaka, H., Hagiwara, S., Shirane, D., Yamakawa, T., Sato, Y., Matsumoto, C., Ishizaki, K., Hishinuma, M., Chida, K., Sasaki, K., et al. (2023) · ACS Nano · doi:10.1021/acsnano.2c10501 · Cited by 44
Engineered mRNA Delivery Systems for Biomedical Applications
Wang, J., Zhu, H., Gan, J., Liang, G., Li, L., & Zhao, Y. (2023) · Advanced Materials · doi:10.1002/adma.202308029 · Cited by 46
Electrochemical Glycosylation via Halogen-Atom-Transfer for C -Glycoside Assembly
Wu, J., Rajeshwaran, P., Kallert, F., Homölle, S. L., & Ackermann, L. (2024) · ACS Catalysis · doi:10.1021/acscatal.4c02322 · Cited by 43
Brook, B., Duval, V., Barman, S., Speciner, L., Sweitzer, C., Khanmohammed, A., Menon, M., Foster, K., Ghosh, P., Abedi, K., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adm8451 · Cited by 49
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
Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses
Castaño, D., Bettini, E., Kumar, B., Chudnovskiy, A., Siv, A., Protti, G., Nakandakari-Higa, S., Ceglia, S., Luna, N. D., Chiu, J. E., et al. (2025) · Cell · doi:10.1016/j.cell.2025.11.023 · Cited by 44
Self-citationAn expanding universe of mRNA modifications
Jaffrey, S. R. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2911 · Cited by 43
In search of the mRNA modification landscape in plants
Chmielowska‐Bąk, J., Arasimowicz‐Jelonek, M., & Deckert, J. (2019) · BMC Plant Biology · doi:10.1186/s12870-019-2033-2 · Cited by 43
Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment
Karim, M. E., Haque, S. T., Al-Busaidi, H., Bakhtiar, A., Tha, K. K., Holl, M. M. B., & Chowdhury, E. H. (2022) · Archives of Pharmacal Research · doi:10.1007/s12272-022-01418-x · Cited by 45
Feeder‐Free Reprogramming of Human Fibroblasts with Messenger RNA
Warren, L. A., & Wang, J. (2013) · Current Protocols in Stem Cell Biology · doi:10.1002/9780470151808.sc04a06s27 · Cited by 42
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 43
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 44
Mechanisms and research advances in mRNA antibody drug-mediated passive immunotherapy
Zhao, Y., Gan, L., Ke, D., Chen, Q., & Fu, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04553-1 · Cited by 45
Therapeutic synthetic and natural materials for immunoengineering
Slezak, A., Chang, K., Hossainy, S., Mansurov, A., Rowan, S. J., Hubbell, J. A., & Guler, M. O. (2024) · Chemical Society Reviews · doi:10.1039/d3cs00805c · Cited by 44
Abdelaziz, K., Helmy, Y. A., Yitbarek, A., Hodgins, D. C., Sharafeldin, T. A., & Selim, M. H. (2024) · Vaccines · doi:10.3390/vaccines12020134 · Cited by 47
Current Analytical Strategies for mRNA-Based Therapeutics
Camperi, J., Chatla, K., Freund, E. C., Galan, C., Lippold, S., & Guilbaud, A. (2025) · Molecules · doi:10.3390/molecules30071629 · Cited by 47
Current strategies employed in the manipulation of gene expression for clinical purposes
Tsai, H., Pietrobon, V., Peng, M., Wang, S., Zhao, L., Marincola, F. M., & Cai, Q. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03747-3 · Cited by 48
Gregory, G. L., & Copple, I. M. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.12.016 · Cited by 43
Miller, M. G., Alvizo, O., Baskerville, S., Chintala, A., Chng, C., Dassie, J. P., Dorigatti, J. D., Huisman, G. W., Jenne, S., Kadam, S., et al. (2024) · Faraday Discussions · doi:10.1039/d4fd00023d · Cited by 42
Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases
Wu, J., Wang, H., Gao, P., & Ouyang, S. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.06.026 · Cited by 43
Nanotechnology for immuno-oncology
Grippin, A., Lee, D., Parkes, E. E., Jiang, W., & Kim, B. Y. S. (2025) · Nature Cancer · doi:10.1038/s43018-025-01025-x · Cited by 48
Plowright, A. T., Engkvist, O., Gill, A. L., Knerr, L., & Wang, Q. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307034 · Cited by 41
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
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 42
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 42
Strenkowska, M., Kowalska, J., Łukaszewicz, M., Zuberek, J., Su, W., Rhoads, R. E., Darżynkiewicz, E., & Jemielity, J. (2010) · New Journal of Chemistry · doi:10.1039/b9nj00644c · Cited by 42
Building a community to engineer synthetic cells and organelles from the bottom-up
Staufer, O., Lora, J. A. D., Bailoni, E., Bazrafshan, A. S., Benk, A. S., Jahnke, K., Manzer, Z. A., Otrin, L., Pérez, T. D., Sharon, J., et al. (2021) · eLife · doi:10.7554/elife.73556 · Cited by 40
Warmiński, M., Trepkowska, E., Śmietański, M., Sikorski, P. J., Baranowski, M. R., Bednarczyk, M., Kędzierska, H., Majewski, B., Mamot, A., Papiernik, D., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c12629 · Cited by 43
Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung
Valeur, E., Guéret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., Waldmann, H., Grossmann, T. N., & Plowright, A. T. (2017) · Angewandte Chemie · doi:10.1002/ange.201611914 · Cited by 40
Miller, J. B., & Siegwart, D. J. (2018) · Nano Research · doi:10.1007/s12274-018-2099-4 · Cited by 41
Knudson, C. J., Alves-Peixoto, P., Muramatsu, H., Stotesbury, C., Tang, L., Lin, P. J. C., Tam, Y. K., Weissman, D., Pardi, N., & Sigal, L. J. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.05.011 · Cited by 39
Self-citationAn mRNA vaccine to prevent genital herpes
Awasthi, S., & Friedman, H. M. (2021) · Translational research · doi:10.1016/j.trsl.2021.12.006 · Cited by 41
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 41
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
SARS-CoV-2 Vaccine Development: An Overview and Perspectives
Liu, Y., Wang, K., Massoud, T. F., & Paulmurugan, R. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00109 · Cited by 40
State‐of‐the‐art 2023 on gene therapy for phenylketonuria
Martinez, M., Harding, C. O., Schwank, G., & Thöny, B. (2023) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12651 · Cited by 40
SARS-CoV-2 vaccines in patients with SLE
Tang, W., Askanase, A., Khalili, L., & Merrill, J. T. (2021) · Lupus Science & Medicine · doi:10.1136/lupus-2021-000479 · Cited by 39
Production and Evaluation of Nucleoside-Modified mRNA Vaccines for Infectious Diseases
Vadovics, M., Muramatsu, H., Sárközy, A., & Pardi, N. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3770-8_7 · Cited by 40
Self-citationRamadan, E., Ismeal, A. A. A., & Naguib, Y. W. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14111092 · Cited by 42
Prophylactic and therapeutic vaccine development: advancements and challenges
Weerarathna, I. N., Doelakeh, E. S., Kiwanuka, L., Kumar, P., & Arora, S. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00222-x · Cited by 47
Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines
Krawczyk, P. S., Mazur, M., Orzeł, W., Gewartowska, O., Jeleń, S., Antczak, W., Kasztelan, K., Brouze, A., Matylla-Kulińska, K., Gumińska, N., et al. (2025) · Nature · doi:10.1038/s41586-025-08842-1 · Cited by 40
Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics
Kuhn, A. N., Diken, M., Kreiter, S., Vallazza, B., Türeci, Ö., & Sahin, U. (2011) · RNA Biology · doi:10.4161/rna.8.1.13767 · Cited by 39
Modified mRNA as a therapeutic tool to induce cardiac regeneration in ischemic heart disease
Hadas, Y., Katz, M. G., Bridges, C. R., & Zangi, L. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1367 · Cited by 37
A mark of disease: how mRNA modifications shape genetic and acquired pathologies
Destefanis, E., Avşar, G., Groza, P., Romitelli, A., Torrini, S., Pir, P., Conticello, S. G., Aguiló, F., & Dassi, E. (2020) · RNA · doi:10.1261/rna.077271.120 · Cited by 38
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
Tricks and threats of RNA viruses – towards understanding the fate of viral RNA
Markiewicz, Ł., Drążkowska, K., & Sikorski, P. J. (2021) · RNA Biology · doi:10.1080/15476286.2021.1875680 · Cited by 39
Pharma 4.0 Continuous mRNA Drug Products Manufacturing
Ouranidis, A., Davidopoulou, C., Tashi, R., & Kachrimanis, K. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13091371 · Cited by 38
Qin, Z., Bouteau, A., Herbst, C., & Igyártó, B. Z. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010830 · Cited by 51
DeFrancesco, L. (2017) · Nature Biotechnology · doi:10.1038/nbt.3812 · Cited by 40
Nanovaccines for cancer immunotherapy: Focusing on complex formation between adjuvant and antigen
Goradel, N. H., Nemati, M., Bakhshandeh, A., Arashkia, A., & Negahdari, B. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109887 · Cited by 37
In Vitro Synthesis of Modified mRNA for Induction of Protein Expression in Human Cells
Avci‐Adali, M., Behring, A., Steinle, H., Keller, T., Krajeweski, S., Schlensak, C., & Wendel, H. P. (2014) · Journal of Visualized Experiments · doi:10.3791/51943 · Cited by 41
Mamot, A., Sikorski, P. J., Warmiński, M., Kowalska, J., & Jemielity, J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201709052 · Cited by 38
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 38
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
Reverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids
Pfeiffer, M., & Nidetzky, B. (2020) · Nature Communications · doi:10.1038/s41467-020-20035-0 · Cited by 37
The Key Role of Nucleic Acid Vaccines for One Health
Fomsgaard, A., & Liu, M. A. (2021) · Viruses · doi:10.3390/v13020258 · Cited by 37
Svitkin, Y. V., Gingras, A., & Sonenberg, N. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1241 · Cited by 38
Microneedle systems for delivering nucleic acid drugs
Noh, I., Lee, K., & Rhee, Y.-S. (2022) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-021-00558-4 · Cited by 40
The Repeated Setbacks of HIV Vaccine Development Laid the Groundwork for SARS-CoV-2 Vaccines
Harris, J. E. (2021) · National Bureau of Economic Research · doi:10.3386/w28587 · Cited by 37
Aboshi, M., Matsuda, K., Kawakami, D., Kono, K., Kazami, Y., Sekida, T., Komori, M., Morey, A. L., Suga, S., Smith, J. F., et al. (2024) · iScience · doi:10.1016/j.isci.2024.108964 · Cited by 36
Kwok, D. W., & Okada, H. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03450-7 · Cited by 36
Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity
Provine, N. M., & Klenerman, P. (2022) · European Journal of Immunology · doi:10.1002/eji.202250022 · Cited by 37
Mohammadi, Y., Nezafat, N., Negahdaripour, M., Eskandari, S., & Zamani, M. (2022) · Immunologic Research · doi:10.1007/s12026-022-09351-3 · Cited by 38
Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection
Kackos, C. M., DeBeauchamp, J., Davitt, C. J. H., Lonzarić, J., Sealy, R. E., Hurwitz, J. L., Samsa, M. M., & Webby, R. J. (2023) · npj Vaccines · doi:10.1038/s41541-023-00752-5 · Cited by 38
Internal cap-initiated translation for efficient protein production from circular mRNA
Fukuchi, K., Nakashima, Y., Abe, N., Kimura, S., Hashiya, F., Shichino, Y., Liu, Y., Ogisu, R., Sugiyama, S., Kawaguchi, D., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-025-02561-8 · Cited by 42
Engel, N. W., Steinfeld, I., Ryan, D., Anupindi, K., Kim, S., Wellhausen, N., Chen, L., Wilkins, K., Baker, D. J., Rommel, P. C., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2427216122 · Cited by 39
Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART
Peterson, C. W., Younan, P. M., Jerome, K. R., & Kiem, H.-P. (2013) · Gene Therapy · doi:10.1038/gt.2012.98 · Cited by 37
Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation
Yousefi, S., Sharma, S. K., Stojkov, D., Germič, N., Aeschlimann, S., Ge, M. Q., Flayer, C. H., Larson, E. D., Redai, I. G., Zhang, S., et al. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ab1117-455r · Cited by 36
Self-citationThe Current Status of COVID-19 Vaccines
Lundstrom, K. H. (2020) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.579297 · Cited by 35
Ndeupen, S., Bouteau, A., Herbst, C., Qin, Z., Jacobsen, S., Powers, N. E., Hutchins, Z., Kurup, D., Diba, L. Z., Watson, M., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010255 · Cited by 36
Demystifying 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 39
The role of RNA modification in hepatocellular carcinoma
Feng, Q., Wang, D., Xue, T., Lin, C., Gao, Y., Sun, L., Jin, Y., & Liu, D. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.984453 · Cited by 37
Current advances of CRISPR-Cas technology in cell therapy
Qiu, H.-Y., Ji, R.-J., & Zhang, Y. (2022) · Cell Insight · doi:10.1016/j.cellin.2022.100067 · Cited by 38
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
Yim, E. Y., Zhou, A. C., Yim, Y. C., Wang, X., & Xia, T. (2023) · BMEMat · doi:10.1002/bmm2.12060 · Cited by 35
Chen, X., Yuan, Y., Zhou, F., Li, L., Pu, J., & Jiang, X. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06221-y · Cited by 43
Efficient expression of stabilized mRNA PEG-peptide polyplexes in liver
Crowley, S. T., Poliskey, J. A., Baumhover, N. J., & Rice, K. G. (2015) · Gene Therapy · doi:10.1038/gt.2015.68 · Cited by 35
Generation of human induced pluripotent stem cells using non-synthetic mRNA
Rohani, L., Fabian, C., Holland, H., Naaldijk, Y., Dressel, R., Loeffler‐Wirth, H., Binder, H., Arnold, A., & Stolzing, A. (2016) · Stem Cell Research · doi:10.1016/j.scr.2016.03.008 · Cited by 39
Conversion of adult human fibroblasts into neural precursor cells using chemically modified mRNA
Connor, B. J., Firmin, E., McCaughey‐Chapman, A., Monk, R., Lee, K. C., Liot, S., Geiger, J. P., Rudolph, C., & Jones, K. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00918 · Cited by 35
Vaccines to prevent genital herpes
Egan, K. P., Hook, L. M., LaTourette, P., Desmond, A., Awasthi, S., & Friedman, H. M. (2020) · Translational research · doi:10.1016/j.trsl.2020.03.004 · Cited by 37
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 36
Cytidine Acetylation Yields a Noninflammatory Synthetic Messenger RNA
Nance, K. D., Gamage, S. T., Alam, M. M., Yang, A., Levy, M. J., Link, C. N., Florens, L. A., Washburn, M. P., Gu, S., Oppenheim, J. J., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.07.003 · Cited by 35
Influenza Viruses: Innate Immunity and mRNA Vaccines
Lee, S., & Ryu, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.710647 · Cited by 36
Complete Chemical Synthesis of Minimal Messenger RNA by Efficient Chemical Capping Reaction
Abe, N., Imaeda, A., Inagaki, M., Li, Z., Kawaguchi, D., Onda, K., Nakashima, Y., Uchida, S., Hashiya, F., Kimura, Y., et al. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.1c00996 · Cited by 35
Zhang, Q., Wang, M., Han, C., Wen, Z., Meng, X., Qi, D., Wang, N., Du, H., Wang, J., Lu, L., et al. (2023) · Vaccines · doi:10.3390/vaccines11030673 · Cited by 35
Ronk, A. J., Lloyd, N. M., Zhang, M., Atyeo, C. G., Perrett, H. R., Mire, C. E., Hastie, K. M., Sanders, R. W., Brouwer, P. J. M., Saphire, E. O., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41376-6 · Cited by 36
Panova, E. A., Kleymenov, D. A., Shcheblyakov, D. V., Bykonia, E. N., Mazunina, E. P., Dzharullaeva, A. S., Zolotar, A. N., Derkaev, A. A., Esmagambetov, I. B., Sorokin, I. I., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1098302 · Cited by 35
Metadata
- Authors
- Karikó, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S., & Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- Rockefeller University (US)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Corresponding author
- Karikó, Katalin
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 16
- Issue
- 11
- Pages
- 1833-1840
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2775451
- OpenAlex
- W2058647478
- Cited by
- 1,930
- References
- 30
- Citations by year
- 2026: 249 · 2025: 304 · 2024: 279 · 2023: 249 · 2022: 233 · 2021: 227 · 2020: 97 · 2019: 57 · 2018: 58 · 2017: 40 · 2016: 39 · 2015: 37 · 2014: 17 · 2013: 22 · 2012: 11
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- University of California, Riverside
- National Heart, Lung, and Blood Institute (R42HL087688, HL87688)
- National Institute of Allergy and Infectious Diseases (R01AI050484, AI050484)
- National Institute of Neurological Disorders and Stroke (NS29331, R01NS029331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- 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
- Keywords
- pseudouridine, mRNA modification, nucleoside modification, in vitro transcribed mRNA, interferon-alpha, mRNA stability, translational capacity, mRNA vaccines, gene replacement therapy, intravenous delivery
- MeSH terms
- Animals, Cell Line, Genetic Vectors, Humans, Luciferases, Pseudouridine, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
