mRNA vaccines manufacturing: challenges and bottlenecks
Open accessAbstract
Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders. The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step in vitro reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.
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Previous studies showed that the protein yield of mRNA purified by reverse phase HPLC increases by 10-1000 times.
“Previous studies showed that the protein yield of mRNA purified by reverse phase HPLC increases by 10–1000 times.156,453”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [453]
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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
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 · cited 2× · see citing works
“[16] showed that proteins can be produced from in vitro transcribed mRNA in live tissues, mRNA vaccines have been demonstrating efficacy in a number of applications [58].”
BackgroundAn mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., McCullough, M. P., Chappell, J. D., Denison, M. R., Stevens, L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022483 · Cited by 3,237 · 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
The COVID-19 vaccine development landscape
Le, T. T., Andreadakis, Z., Kumar, A., Román, R. G., Tollefsen, S., Saville, M. K., & Mayhew, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-020-00073-5 · Cited by 1,959 · 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
Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Raabe, V., Bailey, R., Swanson, K. A., et al. (2020) · doi:10.1101/2020.06.30.20142570 · Cited by 1,569 · see citing works
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults
Anderson, E. J., Rouphael, N. G., Widge, A. T., Jackson, L. A., Roberts, P. C., Makhene, M., Chappell, J. D., Denison, M. R., Stevens, L. J., Pruijssers, A. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2028436 · Cited by 1,523 · see citing works
mRNA stability in mammalian cells
Ross, J. (1995) · Microbiological Reviews · doi:10.1128/mr.59.3.423-450.1995 · Cited by 1,324 · see citing works
Vaccination greatly reduces disease, disability, death and inequity worldwide
Fe, A., Booy, R., Bock, H. L., Clemens, J. D., Datta, S., John, T. J., Lee, B. W., Lolekha, S., Peltola, H., Ruff, T., et al. (2008) · Bulletin of the World Health Organization · doi:10.2471/blt.07.040089 · Cited by 1,261 · 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
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
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.2.465 · Cited by 915 · see citing works
Modified mRNA vaccines protect against zika virus infection
Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.017 · Cited by 909 · see citing works
Karikó, K., Muramatsu, H., Ludwig, J., & Weissman, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr695 · Cited by 898 · see citing works
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
Zika 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
Beatty, G. L., Haas, A. R., Maus, M. V., Torigian, D. A., Soulen, M. C., Plesa, G., Chew, A., Zhao, Y., Levine, B. L., Albelda, S. Μ., et al. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0170 · Cited by 867 · see citing works
Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination
Widge, A. T., Rouphael, N. G., Jackson, L. A., Anderson, E. J., Roberts, P. C., Makhene, M., Chappell, J. D., Denison, M. R., Stevens, L. J., Pruijssers, A. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmc2032195 · Cited by 722 · see citing works
Turning the corner on therapeutic cancer vaccines
Hollingsworth, R. E., & Jansen, K. (2019) · npj Vaccines · doi:10.1038/s41541-019-0103-y · Cited by 689 · see citing works
The mRNA 5′ cap-binding protein eIF4E and control of cell growth
Sonenberg, N., & Gingras, A. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80150-6 · Cited by 673 · see citing works
Plotkin, S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400472111 · Cited by 642 · see citing works
Bahl, K., Senn, J. J., Yuzhakov, O., Bulychev, A., Brito, L. A., Hassett, K. J., Laska, M. E., Smith, M., Almarsson, Ö., Thompson, J., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.035 · Cited by 642 · see citing works
Developing mRNA-vaccine technologies
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622 · see citing works
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · 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
Alberer, M., Gnad-Vogt, U., Hong, H. S., Mehr, K. T., Backert, L., Finak, G., Gottardo, R., Bica, M. A., Garofano, A., Koch, S. D., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31665-3 · Cited by 530 · 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
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
Petsch, B., Schnee, M., Vogel, A. B., Lange, E., Hoffmann, B., Voss, D., Schlake, T., Thess, A., Kallen, K.-J., Stitz, L., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2436 · Cited by 461 · see citing works
Feldman, R. A., Fuhr, R., Smolenov, I., (Mick) Ribeiro, A., Panther, L., Watson, M., Senn, J. J., Smith, M., Almarsson, Ӧ., Pujar, H. S., et al. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.04.074 · Cited by 454 · 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
Jenner, E. (2010) · Harvard Library (Harvard University) · doi:10.5281/zenodo.15162409 · Cited by 392 · 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 · 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
The development of vaccines: how the past led to the future
Plotkin, S. A., & Plotkin, S. L. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2668 · Cited by 334 · see citing works
(1995) · PubMed · Cited by 330 · see citing works
Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients
Xiao, L., Cen, D., Gan, H., Sun, Y., Huang, N., Xiong, H., Jin, Q., Su, L., Liu, X., Wang, K., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.011 · Cited by 329 · see citing works
Kreiter, 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
Kübler, H., Scheel, B., Gnad-Vogt, U., Miller, K., Schultze-Seemann, W., vom Dorp, F., Parmiani, G., Hampel, C., Wedel, S., Trojan, L., et al. (2015) · Journal for Immunotherapy of Cancer · doi:10.1186/s40425-015-0068-y · Cited by 287 · see citing works
From the RNA world to the clinic
Sullenger, B. A., & Nair, S. (2016) · Science · doi:10.1126/science.aad8709 · Cited by 274 · 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
Walther, J., Godawat, R., Hwang, C., et al. (2015) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2015.05.010 · Cited by 238 · 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
Formulation and Delivery Technologies for mRNA Vaccines
Zeng, C., Zhang, C., Walker, P. G., & Dong, Y. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_217 · Cited by 221 · 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
Emerging Technologies for Low‐Cost, Rapid Vaccine Manufacture
Kis, Z., Shattock, R. J., Shah, N., & Kontoravdi, C. (2018) · Biotechnology Journal · doi:10.1002/biot.201800376 · Cited by 209 · see citing works
Sebastian, M., Schröder, A., Scheel, B., Hong, H. S., Muth, A., von Boehmer, L., Zippelius, A., Mayer, F., Reck, M., Atanackovic, D., et al. (2019) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-019-02315-x · Cited by 209 · see citing works
Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes
Gan, L., Fermer, M. L., Carlsson, L. G., Arfvidsson, C., Egnell, A., Rudvik, A., Kjaer, M., Collén, A., Thompson, J. D., Joyal, J. L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08852-4 · Cited by 209 · see citing works
Kwon, H., Kim, M., Seo, Y., Moon, Y. S., Lee, H. J., Lee, K., & Lee, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.11.034 · Cited by 208 · see citing works
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
Li, M., Zhao, M., Fu, Y., Li, Y., Gong, T., Zhang, Z., & Sun, X. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.043 · Cited by 201 · see citing works
Diken, M., Kreiter, S., Selmi, A., Britten, C. M., Huber, C. G., Türeci, Ö., & Şahin, U. (2011) · Gene Therapy · doi:10.1038/gt.2011.17 · Cited by 192 · see citing works
Coolen, A.-L., Lacroix, C., Mercier‐Gouy, P., Delaune, E. A., Monge, C., Exposito, J., & Verrier, B. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.12.019 · Cited by 192 · 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
Dimov, N., Kastner, E., Hussain, M. T., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11533-1 · Cited by 182 · see citing works
HPLC purification of in vitro transcribed long RNA
Weissman, D., Pardi, N., Muramatsu, H., & Karikó, K. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-260-5_3 · Cited by 180 · see citing works
Antimicrobial resistance and the role of vaccines
Bloom, D. E., BLACK, S. B., SALISBURY, D. M., & Rappuoli, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717157115 · Cited by 176 · see citing works
Udhayakumar, V. K., De Beuckelaer, A., McCaffrey, J., McCrudden, C. M., Kirschman, J. L., Vanover, D., Van Hoecke, L., Roose, K., Deswarte, K., De Geest, B. G., et al. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201601412 · Cited by 169 · cited 1× · see citing works
“CPPs systems have proved to improve T-Cell immunity response in vivo [54], modulate innate immune response and enhance protein expression in both DC and human cancer cells in vitro [55,56].”
BackgroundKis, Z., Kontoravdi, C., Shattock, R. J., & Shah, N. (2020) · Vaccines · doi:10.3390/vaccines9010003 · Cited by 161 · see citing works
Fisher, A. C., Kamga, M.-H., Agarabi, C., Brorson, K., Lee, S. L., & Yoon, S. (2019) · Trends in Biotechnology · doi:10.1016/j.tibtech.2018.08.008 · Cited by 158 · see citing works
[4] Synthesis of long, capped transcripts in Vitro by SP6 and T7 RNA polymerases
Yisraeli, J. K., & Melton, D. A. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(89)80090-4 · Cited by 156 · see citing works
Pascolo, S. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.8.1285 · Cited by 152 · see citing works
Qiu, P., Ziegelhoffer, P. R., Sun, J., & Yang, N. S. (1996) · PubMed · Cited by 150 · see citing works
The broad socioeconomic benefits of vaccination
Bloom, D. E., Fan, V. Y., & Sevilla, J. P. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaj2345 · Cited by 148 · see citing works
Mattei, G., Ferretti, C., Tirella, A., Ahluwalia, A. D., & Mattioli‐Belmonte, M. (2015) · Scientific Reports · doi:10.1038/srep14590 · Cited by 148 · see citing works
Vaccine Hesitancy: A Growing Concern
Kennedy, J. (2020) · Pediatric Drugs · doi:10.1007/s40272-020-00385-4 · Cited by 146 · see citing works
Burris, H. A., Patel, M. R., Cho, D. C., Clarke, J. M., Gutierrez, M., Zaks, T. Z., Frederick, J., Hopson, K., Mody, K., Binanti-Berube, A., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.2523 · Cited by 144 · cited 1× · see citing works
“Recent results show that both technologies can be successfully applied to treat melanoma [72], lymphoma [73,74], and solid tumours [75,76].”
BackgroundEaston, L. E., Shibata, Y., & Lukavsky, P. J. (2010) · RNA · doi:10.1261/rna.1862210 · Cited by 143 · see citing works
Large-scale preparation and purification of polyacrylamide-free RNA oligonucleotides
Lukavsky, P. J., & Puglisi, J. D. (2004) · RNA · doi:10.1261/rna.5264804 · Cited by 139 · 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
Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA
Zhao, M., Li, M., Zhang, Z., Gong, T., & Sun, X. (2016) · Drug Delivery · doi:10.3109/10717544.2015.1038856 · Cited by 132 · see citing works
Allard, S. D., Keersmaecker, B. D., de Goede, A. L., Verschuren, E. J., Koetsveld, J., Reedijk, M. L., Wylock, C., Bel, A. V. D., Vandeloo, J., Pistoor, F. H. M., et al. (2011) · Clinical Immunology · doi:10.1016/j.clim.2011.10.010 · Cited by 119 · see citing works
The current challenges for vaccine development
Oyston, P. C. F., & Robinson, K. (2012) · Journal of Medical Microbiology · doi:10.1099/jmm.0.039180-0 · Cited by 119 · see citing works
Sun, N., Ning, B., Hansson, K. M., Bruce, A. C., Seaman, S. A., Zhang, C., Rikard, S. M., DeRosa, C. A., Fraser, C. L., Wågberg, M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35570-6 · Cited by 119 · 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
A general method for rapid and cost-efficient large-scale production of 5′ capped RNA
Fuchs, A.-L., Neu, A., & Sprangers, R. (2016) · RNA · doi:10.1261/rna.056614.116 · Cited by 106 · see citing works
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
Johanning, F. W., Conry, R. M., LoBuglio, A. F., Wright, M., Sumerel, L. A., Pike, M. J., & Curiel, D. T. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.9.1495 · 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
Gandhi, R. T., Kwon, D. S., Macklin, E. A., Shopis, J., McLean, A. P., McBrine, N., Flynn, T., Peter, L. E., Sbrolla, A., Kaufmann, D., et al. (2015) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000000852 · Cited by 95 · see citing works
Advances in RNA vaccines for preventive indications: A case study of a vaccine against rabies
Armbruster, N., Jasny, E., & Petsch, B. (2019) · Vaccines · doi:10.3390/vaccines7040132 · Cited by 95 · see citing works
Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases
Matsui, A., Uchida, S., Ishii, T., Itaka, K., & Kataoka, K. (2015) · Scientific Reports · doi:10.1038/srep15810 · Cited by 93 · see citing works
Lou, B., Koker, S. D., Lau, C. Y. J., Hennink, W. E., & Mastrobattista, E. (2018) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.8b00524 · Cited by 91 · see citing works
A guide to large-scale RNA sample preparation
Baronti, L., Karlsson, H., Marušič, M., & Petzold, K. (2018) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-018-0943-8 · Cited by 87 · see citing works
Replicon RNA Viral Vectors as Vaccines
Lundstrom, K. H. (2016) · Vaccines · doi:10.3390/vaccines4040039 · Cited by 86 · see citing works
Emerging Technologies for Low‐Cost, Rapid Vaccine Manufacture
Kis, Z., Shattock, R. J., Shah, N., & Kontoravdi, C. (2019) · Biotechnology Journal · doi:10.1002/biot.201970055 · Cited by 83 · see citing works
Hung, C., Xu, X., Li, L., Ma, Y., Qiu, J. F., Viley, A. M., Allen, C., Natarajan, P., Shivakumar, R., Peshwa, M. V., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2017.080 · Cited by 81 · see citing works
Steinle, H., Behring, A., Schlensak, C., Wendel, H. P., & Avci‐Adali, M. (2016) · Stem Cells · doi:10.1002/stem.2402 · Cited by 78 · see citing works
Patel, M. R., Bauer, T. M., Jimeno, A., Wang, D., LoRusso, P., Do, K. T., Stemmer, S. M., Maurice-Dror, C., Geva, R., Zacharek, S., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.3092 · Cited by 69 · cited 1× · see citing works
“Recent results show that both technologies can be successfully applied to treat melanoma [72], lymphoma [73,74], and solid tumours [75,76].”
BackgroundMultimodal Chromatography for Purification of Biotherapeutics – A Review
Halan, V., Maity, S., Bhambure, R., et al. (2018) · Current Protein and Peptide Science · doi:10.2174/1389203718666171020103559 · Cited by 66 · see citing works
Conscious coupling: The challenges and opportunities of cascading enzymatic microreactors
Gruber, P., Marques, M. P. C., O'Sullivan, B. P., et al. (2017) · Biotechnology Journal · doi:10.1002/biot.201700030 · Cited by 62 · see citing works
Self-citationKyte, J. A., Aamdal, S., Dueland, S., Sæbøe‐Larssen, S., Inderberg, E. M., Madsbu, U. E., Skovlund, E., Gaudernack, G., & Kvalheim, G. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1232237 · Cited by 59 · see citing works
Design of in vitro Transcribed mRNA Vectors for Research and Therapy
Tusup, M., French, L. E., Matos, M. D., Gatfield, D., Kündig, T. M., & Pascolo, S. (2019) · CHIMIA International Journal for Chemistry · doi:10.2533/chimia.2019.391 · Cited by 54 · 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
mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
Bell, G. D., Yang, Y., Leung, E. Y., & Krissansen, G. W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201464 · Cited by 43 · see citing works
The messenger's great message for vaccination
Pascolo, S. (2015) · Expert Review of Vaccines · doi:10.1586/14760584.2015.1000871 · Cited by 40 · see citing works
Lichtenegger, F. S., Schnorfeil, F. M., Rothe, M., Deiser, K., Altmann, T., Bücklein, V., Köhnke, T., Augsberger, C., Konstandin, N. P., Spiekermann, K., et al. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1117 · Cited by 40 · see citing works
Blakney, A. K., Abdouni, Y., Yilmaz, G., Liu, R., McKay, P. F., Bouton, C. R., Shattock, R. J., & Becer, C. R. (2020) · Biomacromolecules · doi:10.1021/acs.biomac.0c00445 · Cited by 36 · see citing works
Kapoor, Y., Meyer, R. F., Meyer, B. K., et al. (2020) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-019-09426-z · Cited by 31 · see citing works
Mao, H. H., & Chao, S.-B. (2019) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2019_107 · Cited by 30 · see citing works
Cafri, G., Gartner, J. J., Hopson, K., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.2643 · Cited by 28 · see citing works
Drury, G., Jolliffe, S., & Mukhopadhyay, T. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.01.050 · Cited by 21 · see citing works
Considerations for Producing mRNA Vaccines for Clinical Trials
Schmid, A. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6481-9_15 · Cited by 11 · see citing works
Akash, M. S. H., & Rehman, K. (2019) · Springer eBooks · doi:10.1007/978-981-15-1547-7_13 · Cited by 9 · see citing works
Buonaguro, L., Mayer, A., Loeffler, M. W., et al. (2020) · Cancer Research · doi:10.1158/1538-7445.am2020-lb-094 · Cited by 6 · see citing works
Rappuoli, R. (2020) · Cell · doi:10.1016/j.cell.2020.09.039 · Cited by 4 · see citing works
Hoerr, I. (2000) · doi:10.1002/1521-4141(200001)30:1
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Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
A Comprehensive Review of mRNA Vaccines
Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K., Palakurthi, S. S., & Khan, W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032700 · Cited by 457 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
Szabó, G. T., Mahiny, A. J., & Vlatkovic, I. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.016 · Cited by 308 · see citing works
- Authors
- Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M., & Marques, M. P. C.
- Affiliations
- University of Lisbon (PT)
- University College London (GB)
- Corresponding author
- Azevedo, Ana M.
- Marques, Marco P.C.
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 39
- Issue
- 16
- Pages
- 2190-2200
- ISSN
- 0264-410X (ISSN-L)
- PMC
- PMC7987532
- OpenAlex
- W3138708387
- Cited by
- 545
- References
- 109
- Citations by year
- 2026: 92 · 2025: 121 · 2024: 131 · 2023: 102 · 2022: 71 · 2021: 27
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Vaccine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Engineering and Physical Sciences Research Council
- Foundation for Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mRNA vaccines, vaccine production, mass production, in vitro transcription, mRNA purification, DNase digestion, chromatography, cross-flow filtration, COVID-19 vaccines, cost-effectiveness
- MeSH terms
- COVID-19, mRNA Vaccines, Humans, RNA, Messenger, Vaccines, Synthetic, Pandemics
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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.
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