mRNA transcript therapy
Abstract
mRNA is the central molecule of all forms of life. It is generally accepted that current life on Earth descended from an RNA world. mRNA, after its first therapeutic description in 1992, has recently come into increased focus as a method to deliver genetic information. The recent solution to the two main difficulties in using mRNA as a therapeutic, immune stimulation and potency, has provided the basis for a wide range of applications. While mRNA-based cancer immunotherapies have been in clinical trials for a few years, novel approaches; including, in vivo delivery of mRNA to replace or supplement proteins, mRNA-based generation of pluripotent stem cells, or genome engineering using mRNA-encoded meganucleases are beginning to be realized. This review presents the current state of mRNA drug technologies and potential applications, as well as discussing the challenges and prospects in mRNA development and drug discovery.
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Mammalian host cells attack unmodified exogeneous RNA.
“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 [13]
All U nucleotides in the mRNA vaccines have been modified to N1-methyl-pseudouridine (Ψ) to reduce immune reaction towards mRNA and to increase protein production.
“However, all U nucleotides in the mRNA vaccines have been modified to N1-methyl-pseudouridine (Ψ) [14] to reduce immune reaction towards mRNA and to increase protein production [2,13,58].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [13]
Cites
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
Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495 · see citing works
High-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292 · see citing works
Efficient genome editing in zebrafish using a CRISPR-Cas system
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J.-R. J., & Joung, J. K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2501 · Cited by 2,937 · see citing works
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
Self-citationRIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210 · see citing works
AU-rich elements: characterization and importance in mRNA degradation
Chen, C.-Y. A., & Shyu, A.-B. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89102-1 · Cited by 1,948 · see citing works
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
Self-citationA serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency
Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.-L., Fraser, C. C., Cavazzana-Calvo, M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejm200301163480314 · Cited by 1,867 · cited 1× · see citing works
“Unlike DNAbased therapy, mRNA does not have the risk of integration into the chromosomes [3–7], which can lead to insertional mutagenesis with potentially disastrous results [8,9].”
BackgroundMali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., & Church, G. M. (2013) · Nature Biotechnology · doi:10.1038/nbt.2675 · Cited by 1,752 · cited 1× · see citing works
“The RNA tags identify the site for cutting [154,155].”
BackgroundRNAi-mediated gene silencing in non-human primates
Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357 · see citing works
Human iPSC-based modeling of late-onset disease via progerin-induced aging
Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., Mandal, P. K., Vera, E., Shim, J.-W., Kriks, S., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.006 · Cited by 777 · 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
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
Self-citationNonviral delivery of self-amplifying RNA vaccines
Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209367109 · Cited by 675 · cited 11× · see citing works
“Routy JP, Boulassel MR, Yassine-Diab B, et al. Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy.”
BackgroundInfluentialHoltkamp, 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
Weide, B., Pascolo, S., Scheel, B., Derhovanessian, E., Pflugfelder, A., Eigentler, T. K., Pawelec, G., Hoerr, I., Rammensee, H.-G., & Garbe, C. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a00068 · Cited by 378 · cited 1× · see citing works
“Clinical trials using uncomplexed (naked) or protamine-complexed mRNA in vaccines with delivery either by the intradermal route [33–37] or with direct injection into lymph nodes [38–40] are currently ongoing.”
MethodAnderson, 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
Fotin-Mleczek, M., Duchardt, K. M., Lorenz, C., Pfeiffer, R., Ojkić-Zrna, S., Probst, J., & Kallen, K.-J. (2011) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181f7dbe8 · Cited by 335 · cited 3× · see citing works
“Reprogramming of cells DCs: HIV antigens [141-143] Infectious disease vaccines DCs: pancreatic adenocarcinoma [122,123], prostate cancer [124,125], melanoma [126-130], colon cancer [131] renal cell carcinoma [12], melanoma [14] T cells: CAR-Her-2/neo [117], CAR-mesothelin [118,119], CAR-CD19 [120,121] DCs: MUC1[114],…”
BackgroundKreiter, S., Selmi, A., Diken, M., Koslowski, M., Britten, C. M., Huber, C., Türeci, Ö., & Sahin, U. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0699 · Cited by 309 · see citing works
Reversal of Diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA
Jirikowski, G. F., Sanna, P. P., Maciejewski-Lenoir, D., & Bloom, F. E. (1992) · Science · doi:10.1126/science.1546298 · Cited by 282 · 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
Pollard, C., Rejman, J., De Haes, W., Verrier, B., Van Gulck, E., Naessens, T., De Smedt, S., Bogaert, P., Grooten, J., Vanham, G., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2012.202 · Cited by 248 · see citing works
Kuhn, A. N., Diken, M., Kreiter, S., Selmi, A., Kowalska, J., Jemielity, J., Darzynkiewicz, E., Huber, C., Türeci, Ö., & Sahin, U. (2010) · Gene Therapy · doi:10.1038/gt.2010.52 · Cited by 226 · see citing works
Fleeton, M. N., Chen, M., Berglund, P., Rhodes, G., Parker, S. E., Murphy, M., Atkins, G. J., & Liljeström, P. (2001) · The Journal of Infectious Diseases · doi:10.1086/319857 · Cited by 157 · 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
Vaccination with Messenger RNA (mRNA)
Pascolo, S. (2008) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-72167-3_11 · Cited by 126 · see citing works
Shi, B., Keough, E., Matter, A., Leander, K., Young, S., Carlini, E., Sachs, A. B., Tao, W., Abrams, M., Howell, B., et al. (2011) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155411410885 · Cited by 125 · see citing works
Malarkannan, S., Horng, T., Shih, P. P., Schwab, S., & Shastri, N. (1999) · Immunity · doi:10.1016/s1074-7613(00)80067-9 · Cited by 106 · see citing works
Flagged first, then by citations
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Sorted by citations
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
Self-citationCAR T cells produced in vivo to treat cardiac injury
Rurik, J. G., Tombácz, I., Yadegari, A., Méndez Fernández, P. O., Shewale, S. V., Li, L., Kimura, T., Soliman, O. Y., Papp, T. E., Tam, Y. K., et al. (2022) · Science · doi:10.1126/science.abm0594 · Cited by 1,400 · see citing works
Self-citationPardi, N., Tuyishime, S., Muramatsu, H., Kariko, K., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., & Weissman, D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.007 · Cited by 1,014 · see citing works
Self-citationZika virus protection by a single low-dose nucleoside-modified mRNA vaccination
Pardi, N., Hogan, M. J., Pelc, R. S., Muramatsu, H., Andersen, H., DeMaso, C. R., Dowd, K. A., Sutherland, L. L., Scearce, R. M., Parks, R., et al. (2017) · Nature · doi:10.1038/nature21428 · Cited by 884 · see citing works
Self-citationAdvances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
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
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
Pardi, N., Secreto, A. J., Shan, X., Debonera, F., Glover, J., Yi, Y., Muramatsu, H., Ni, H., Mui, B. L., Tam, Y. K., et al. (2017) · Nature Communications · doi:10.1038/ncomms14630 · Cited by 352 · see citing works
Self-citationPrinciples for designing an optimal mRNA lipid nanoparticle vaccine
Kon, E., Elia, U., & Peer, D. (2022) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.09.016 · Cited by 269 · 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
John, S., Yuzhakov, O., Woods, A., Deterling, J., Hassett, K., Shaw, C. A., & Ciaramella, G. (2018) · Vaccine · doi:10.1016/j.vaccine.2018.01.029 · Cited by 229 · see citing works
Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines
Xia, X. (2021) · Vaccines · doi:10.3390/vaccines9070734 · Cited by 201 · see citing works
Lim, S., Khoo, R., Peh, K. M., Teo, J., Chang, S. C., Ng, S., Beilhartz, G. L., Melnyk, R. A., Johannes, C. W., Brown, C. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920251117 · Cited by 170 · see citing works
Nanoscale platforms for messenger RNA delivery
Li, B., Zhang, X., & Dong, Y. (2019) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1530 · Cited by 170 · see citing works
Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency
Prieve, M. G., Harvie, P., Monahan, S. D., Roy, D., Li, A. G., Blevins, T. L., Paschal, A. E., Waldheim, M., Bell, E. C., Galperin, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.12.024 · Cited by 145 · see citing works
Trepotec, Z., Geiger, J., Plank, C., Aneja, M. K., & Rudolph, C. (2019) · RNA · doi:10.1261/rna.069286.118 · Cited by 129 · see citing works
Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases
Trepotec, Z., Lichtenegger, E., Plank, C., Aneja, M. K., & Rudolph, C. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.12.012 · Cited by 115 · see citing works
Systemic mRNA delivery to the lungs by functional polyester-based carriers
Yan, Y., Xiong, H., Zhang, X., Cheng, Q., & Siegwart, D. J. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b01356 · Cited by 111 · see citing works
An overview of rational design of mRNA-based therapeutics and vaccines
To, K. K. W., & Cho, W. C. S. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1935859 · Cited by 110 · see citing works
Recent innovations in mRNA vaccines
Ulmer, J. B., & Geall, A. J. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.05.008 · Cited by 91 · see citing works
Zhang, C., Zhang, X., Zhao, W., Zeng, C., Li, W., Li, B., Luo, X., Li, J., Jiang, J., Deng, B., et al. (2019) · Nano Research · doi:10.1007/s12274-019-2308-9 · Cited by 61 · see citing works
Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens
Poveda, C., Biter, A. B., Bottazzi, M. E., & Strych, U. (2019) · Vaccines · doi:10.3390/vaccines7040131 · Cited by 54 · see citing works
Jagger, B. W., Dowd, K. A., Chen, R. E., Desai, P., Foreman, B., Burgomaster, K. E., Himansu, S., Kong, W.-P., Graham, B. S., Pierson, T. C., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz338 · Cited by 53 · see citing works
Tam, Y. K., Madden, T. D., & Hope, M. J. (2016) · Journal of Drug Targeting · doi:10.1080/1061186x.2016.1221955 · Cited by 20 · see citing works
- Authors
- Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Weissman, Drew
- ORCID
- Weissman, Drew
- Venue
- Expert Review of Vaccines
- Publisher
- Informa UK Limited
- Published
- 2014-10-31
- Volume
- 14
- Issue
- 2
- Pages
- 265-281
- ISSN
- 1476-0584 (ISSN-L)
- 1744-8395
- OpenAlex
- W1986939156
- Cited by
- 228
- References
- 29
- Citations by year
- 2026: 12 · 2025: 36 · 2024: 27 · 2023: 34 · 2022: 32 · 2021: 29 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 8 · 2016: 5 · 2015: 3
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Review of Vaccines (publishedVersion)
- PubMed (publishedVersion)
- 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, mRNA vaccines, cancer immunotherapy, genome editing, immunostimulation, drug discovery
- MeSH terms
- Humans, Immunotherapy, Proteins, Pseudouridine, RNA, Messenger, Technology, Pharmaceutical, Drug Design, Genetic Therapy, Drug Delivery Systems, Vaccines, DNA, RNA Stability, Pluripotent Stem Cells, Drug Discovery
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