The promise of mRNA vaccines: a biotech and industrial perspective
Open accessAbstract
mRNA technologies have the potential to transform areas of medicine, including the prophylaxis of infectious diseases. The advantages for vaccines range from the acceleration of immunogen discovery to rapid response and multiple disease target manufacturing. A greater understanding of quality attributes that dictate translation efficiency, as well as a comprehensive appreciation of the importance of mRNA delivery, are influencing a new era of investment in development activities. The application of translational sciences and growing early-phase clinical experience continue to inform candidate vaccine selection. Here we review the state of the art for the prevention of infectious diseases by using mRNA and pertinent topics to the biotechnology and pharmaceutical industries.
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mRNA-based therapy is an effective platform for treatment of infectious diseases and cancer.
“Messenger RNA (mRNA)-based therapy recently emerged as an effective platform for treatment of infectious diseases and cancer (Jackson et al., 2020; Mascola and Fauci, 2020).”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Jackson et al., 2020
The Introduction describes mRNA vaccines as a platform for preventing infectious diseases, but says clinical efficacy and safety remain to be proven. The Summary likewise describes potential advantages rather than established effectiveness. These passages do not support the claim that mRNA therapy is already effective for treating infectious diseases or cancer; the paper does not address cancer treatment. (LLM, conf=0.87)
Experimental — accuracy not yet measuredmRNA vaccines still suffer from decreased efficacy due to poor RNA stability in solution and in vivo and to limited expression of the payload mRNA.
“mRNA vaccines still suffer from decreased efficacy due to poor RNA stability in solution and in vivo and to limited expression of the payload mRNA; these are all pivotal issues that need to be carefully optimized for preclinical and clinical applications3–6.”
From Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics (2022) · cites this paper as [4]
The “State-of-the-art” section says mRNA is susceptible to degradation during delivery and that construct quality affects expression. “Perspective #1” links improved stability and expression to greater antigen production and potential potency. The cited paper does not specifically establish poor stability in solution as a cause of decreased vaccine efficacy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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“58 Therefore, safety and tolerability may limit multi-antigen approaches, and here translational sciences are crucial for development.”
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“30, 31 In addition to optimizing an mRNA construct, and of quintessential importance, is the delivery of the mRNA vaccine from the bolus at the injection site into the cytoplasm of cells for the initiation of translation.”
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“The addition of the 5′ cap and the 3′ poly(A) tail can be achieved during the in vitro transcription step 7, 8 or enzymatically after transcription.”
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“59 Systems biology techniques can help in the understanding of fine differences between various NRM and SAM vaccine sequences, as well as serving as useful tools to frame sequence optimizations during iterative development schemes.”
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“51 Improved stability of mRNA can also be achieved through various modifications of the triphosphate bridge within the cap structure.”
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BackgroundExtracellular RNA sensing by pattern recognition receptors
Tatematsu, M., Funami, K., Seya, T., & Matsumoto, M. (2018) · Journal of Innate Immunity · doi:10.1159/000494034 · Cited by 90 · cited 1× · see citing works
“Thus, early-phase clinical trials need to be designed in a way to appropriately capture the inflammatory component intrinsic to all mRNA vaccines, given that several intracellular innate immune response sensors are activated by RNA. 65 Elements include measuring administration site reactions such as pain, tenderness-a…”
BackgroundCheng, W., Hung, C., Chai, C., Hsu, K., He, L., Ling, M. F., & Wu, T. ‐. (2001) · Journal of Virology · doi:10.1128/jvi.75.5.2368-2376.2001 · Cited by 86 · cited 2× · see citing works
“4, 5 Generally, the ORF encoding viral structural proteins is replaced by the selected transcript of interest, and the viral RNA-dependent RNA polymerase is retained to direct cytoplasmic amplification of the replicon construct.”
BackgroundDiscrimination of cytosolic self and non-self RNA by RIG-I-like receptors
Lässig, C., & Hopfner, K. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.788398 · Cited by 76 · cited 1× · see citing works
“[16] [17] [18] In addition, 2-O′-unmethylated capped RNA can be sequestered by cellular IFN-induced proteins with tetratricopeptide repeats (IFIT1) that prevent the initiation of translation, 19 or detected by the cytoplasmic RNA sensor MDA5.”
BackgroundArginase I mRNA therapy – a novel approach to rescue arginase 1 enzyme deficiency
Asrani, K. H., Cheng, L., Cheng, C. J., & Subramanian, R. R. (2018) · RNA Biology · doi:10.1080/15476286.2018.1475178 · Cited by 58 · cited 1× · see citing works
“[34] [35] [36] There have been numerous examples of successful delivery of mRNA by using LNPs for therapeutic [37] [38] [39] [40] as well as vaccine applications.”
BackgroundJagger, 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
Rydzik, A. M., Warmiński, M., Sikorski, P. J., Baranowski, M. R., Walczak, S., Kowalska, J., Zuberek, J., Łukaszewicz, M., Nowak, E., Claridge, T. D. W., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx569 · Cited by 32 · cited 1× · see citing works
“[52] [53] [54] Optimization of the carrier system can provide significant benefit as well.”
BackgroundSafety and immunogenicity of a mRNA-based chikungunya vaccine in a phase 1 dose-ranging trial
Shaw, C. A., Panther, L., August, A., Zaks, T. Z., Smolenov, I. V., Bart, S., & Watson, M. (2019) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2018.11.058 · Cited by 32 · see citing works
Human challenge models: tools to accelerate the development of malaria vaccines
Cooper, M. M., Loiseau, C., McCarthy, J., & Doolan, D. (2019) · Expert Review of Vaccines · doi:10.1080/14760584.2019.1580577 · Cited by 28 · cited 1× · see citing works
“60 Further, the use of functional assessments, like human challenge models, 61 where the immunologic profiles of the participants and the specific details of the challenge strain(s) are well characterized-an approach mostly used to date in the evaluation of more traditional vaccinesprovides an important and powerful m…”
BackgroundMoving from Empirical to Rational Vaccine Design in the ‘Omics’ Era
Sharma, M., Krammer, F., García‐Sastre, A., & Tripathi, S. (2019) · Vaccines · doi:10.3390/vaccines7030089 · Cited by 27 · see citing works
Current Status of Messenger RNA Delivery Systems
Stanton, M. G. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0726 · Cited by 25 · cited 1× · see citing works
“[34] [35] [36] There have been numerous examples of successful delivery of mRNA by using LNPs for therapeutic [37] [38] [39] [40] as well as vaccine applications.”
Background
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Research works printed but not linked: 1
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Mechanisms of SARS-CoV-2 entry into cells
Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00418-x · Cited by 3,082 · see citing works
mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability
Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W., & Crommelin, D. J. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120586 · Cited by 1,566 · see citing works
“After identification of the protective protein antigen(s) and sequencing the corresponding gene(s), the mRNA can be made within weeks (Jackson et al., 2020).”
Immunological considerations for COVID-19 vaccine strategies
Jeyanathan, M., Afkhami, S., Smaill, F., Miller, M. S., Lichty, B. D., & Xing, Z. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-00434-6 · Cited by 1,015 · see citing works
The clinical progress of mRNA vaccines and immunotherapies
Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R., & Anderson, D. G. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01294-2 · Cited by 823 · see citing works
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 801 · see citing works
A thermostable mRNA vaccine against COVID-19
Zhang, N.-N., Li, X.-F., Deng, Y.-Q., Zhao, H., Huang, Y.-J., Yang, G., Huang, W.-J., Gao, P., Zhou, C., Zhang, R.-R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.024 · Cited by 671 · see citing works
“Messenger RNA (mRNA)-based therapy recently emerged as an effective platform for treatment of infectious diseases and cancer (Jackson et al., 2020; Mascola and Fauci, 2020).”
Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants
Qu, L., Yi, Z., Shen, Y., Lin, L., Chen, F., Xu, Y., Wu, Z., Tang, H., Zhang, X., Tian, F., et al. (2021) · doi:10.1101/2021.03.16.435594 · Cited by 636 · see citing works
Lipid nanoparticles for nucleic acid delivery: Current perspectives
Samaridou, E., Heyes, J. A., & Lutwyche, P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.002 · Cited by 593 · see citing works
Multifunctional biomolecule nanostructures for cancer therapy
Wang, J., Li, Y., & Nie, G. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00315-x · Cited by 505 · 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
Parayath, N. N., Stephan, S. B., Koehne, A. L., Nelson, P. S., & Stephan, M. T. (2020) · Nature Communications · doi:10.1038/s41467-020-19486-2 · Cited by 448 · see citing works
mRNA vaccine: a potential therapeutic strategy
Wang, Y., Zhang, Z., Luo, J., Han, X., Wei, Y., & Wei, X. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01311-z · Cited by 422 · see citing works
Vaccine development for emerging infectious diseases
Excler, J., Saville, M. K., Berkley, S., & Kim, J. H. (2021) · Nature Medicine · doi:10.1038/s41591-021-01301-0 · Cited by 409 · 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
“2; Thermo Fisher Scientific-Gibco 20012027) at 50 °C without added MgCl2; and (4) PBS (pH 7.”
BackgroundCombinatorial 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
A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development
Li, Y., Tenchov, R., Smoot, J., Liu, C., Watkins, S., & Zhou, Q. A. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00120 · Cited by 345 · see citing works
Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review)
Călina, D. C., Docea, A. O., Petrakis, D., Egorov, A. M., Ishmukhametov, A. A., Gabibov, A., Штильман, М. И., Kostoff, R. N., Carvalho, F. D., Vinceti, M., et al. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4596 · Cited by 319 · see citing works
“The mRNA (encoding RiboNucleic Acid) vaccine encodes a stable prefused form (the form before being fused to the cell membrane of the host cell) of Spike protein (S) (63).”
BackgroundThe interaction of innate immune and adaptive immune system
Wang, R., Lan, C., Benlagha, K., Câmara, N. O. S., Miller, H. E., Kubo, M., Heegaard, S., Lee, P. P. W., Yang, L., Forsman, H. F., et al. (2024) · MedComm · doi:10.1002/mco2.714 · Cited by 355 · see citing works
“267 In contrast to DNA vaccines, mRNA vaccines mitigate the risk of insertional mutagenesis in the host genome and can modulate antigen expression.”
BackgroundmRNA vaccines for COVID-19: what, why and how
Park, J. W., Lagniton, P. N. P., Liu, Y., & Xu, R.-H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59233 · Cited by 321 · see citing works
Suzuki, Y., & Ishihara, H. (2021) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100424 · Cited by 304 · see citing works
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
“The use of mRNA vaccines for pandemic response has been well described previously in preclinical[12-25] and clinical settings,[16] but this is the first time we have seen the platforms deployed in a real pandemic setting.”
BackgroundDNA vaccines against COVID-19: Perspectives and challenges
Silveira, M. M., Moreira, G. M. S. G., & Mendonça, M. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118919 · Cited by 285 · see citing works
“Thus, the mode of application and effectiveness of mRNA vaccines may be increased [65].”
Jung, H. N., Lee, S.-Y., Lee, S., Youn, H., & Im, H.-J. (2022) · Theranostics · doi:10.7150/thno.77259 · Cited by 282 · see citing works
“In addition, various mRNA engineering methods have been developed to enhance the stability and the translation efficacy of mRNA therapeutics, such as a selection of untranslated regions (UTRs), addition of a poly-A tail, capping, and nucleoside modification [6].”
MethodThe Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines
Morais, P., Adachi, H., & Yu, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.789427 · Cited by 274 · see citing works
“This technology made possible a fast pace of discovery and manufacturing, critical features that could be fully utilized in a biotech and pharmaceutical setting (Jackson et al., 2020).”
BackgroundCircular RNA vaccine in disease prevention and treatment
Niu, D., Wu, Y., & Lian, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01561-x · Cited by 273 · see citing works
Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy
Guevara, M. L., Persano, F., & Persano, S. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.589959 · Cited by 257 · see citing works
“It has been shown that DNA-dependent RNA polymerases yield abortive initiation products, as well as double-stranded RNA resulting from self-complementary, which can lead to type I IFN and inflammatory cytokines production upon pattern recognition receptors recognition (Jackson et al., 2020).”
BackgroundKim, S. C., Sekhon, S. S., Shin, W.-R., Ahn, G., Cho, B.-K., Ahn, J.-Y., & Kim, Y.-H. (2022) · Molecular & Cellular Toxicology · doi:10.1007/s13273-021-00171-4 · Cited by 255 · see citing works
Li, Y., Ma, X., Yue, Y., Zhang, K., Cheng, K., Feng, Q., Ma, N., Liang, J., Zhang, T., Zhang, L., et al. (2022) · Advanced Materials · doi:10.1002/adma.202109984 · Cited by 247 · see citing works
mRNA vaccines in disease prevention and treatment
Zhang, G., Tang, T., Chen, Y., Huang, X., & Liang, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01579-1 · Cited by 253 · see citing works
Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies
Li, H., Peng, K., Yang, K., Ma, W., Qi, S., Yu, X., He, J., Lin, X., & Yu, G. (2022) · Theranostics · doi:10.7150/thno.77350 · Cited by 245 · see citing works
“Previous strategies to increase the stability of mRNA molecules include the optimization of untranslated regions such as 5’ and 3’ translation regulating sequences, incorporation of a methylguanosine cap analog to protect mRNA from decapping enzymes, nucleoside modifications, and codon optimization [23-25].”
MethodLipid Nanoparticles as Delivery Systems for RNA-Based Vaccines
Aldosari, B. N., Alfagih, I. M., & Almurshedi, A. S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020206 · Cited by 242 · see citing works
An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts
Dousis, A. D., Ravichandran, K. R., Hobert, E. M., Moore, M. J., & Rabideau, A. E. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01525-6 · Cited by 238 · see citing works
Chu, L., McPhee, R. A., Huang, W., Bennett, H., Pajón, R., Nestorova, B., & Leav, B. A. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.02.007 · Cited by 225 · see citing works
“Vaccines developed based on mRNA technology can be rapidly engineered and scaled-up, offering accelerated timelines to determine efficacy compared to more traditional approaches [10,11].”
The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case
Blenke, E. O., Örnskov, E., Schöneich, C., Nilsson, G. Å., Volkin, D. B., Mastrobattista, E., Almarsson, Ö., & Crommelin, D. J. A. (2022) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2022.11.001 · Cited by 214 · see citing works
Aldrich, C., Leroux–Roels, I., Huang, K. B., Bica, M. A., Loeliger, E., Schoenborn-Kellenberger, O., Walz, L., Leroux-Roels, G., von Sonnenburg, F., & Oostvogels, L. (2021) · Vaccine · doi:10.1016/j.vaccine.2020.12.070 · Cited by 204 · see citing works
Kremsner, P., Mann, P., Bosch, J., Fendel, R., Gabor, J. J., Kreidenweiss, A., Kroidl, A., Leroux-Roels, I., Leroux-Roels, G., Schindler, C., et al. (2020) · doi:10.1101/2020.11.09.20228551 · Cited by 199 · see citing works
de Alwis, R., Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Low, J. G. H., Kalimuddin, S., Matsuda, D., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.001 · Cited by 191 · see citing works
Whitley, J., Zwolinski, C., Denis, C., Maughan, M., Hayles, L., Clarke, D., Snare, M., Liao, H., Chiou, S., Marmura, T., et al. (2021) · Translational research · doi:10.1016/j.trsl.2021.11.009 · Cited by 178 · see citing works
“LNP formulations containing novel ionizable cationic lipids are the current leaders in the RNA delivery field with successful application in the delivery of small interfering RNA (siRNA), as well as mRNAs encoding vaccine antigens and therapeutic proteins.(8,9) The work described here utilizes the non replicating mRNA…”
Delivery Strategies for mRNA Vaccines
Ramachandran, S., Satapathy, S. R., & Dutta, T. (2022) · Pharmaceutical Medicine · doi:10.1007/s40290-021-00417-5 · Cited by 182 · see citing works
“Third, mRNAs can be rapidly and inexpensively synthesized with high yield through in vitro transcription reaction and hence are easily scalable to kilogram level quantity [17, 18].”
BackgroundKremsner, P. G., Ahuad Guerrero, R. A., Arana-Arri, E., Aroca Martinez, G. J., Bonten, M., Chandler, R., Corral, G., De Block, E. J. L., Ecker, L., Gabor, J. J., et al. (2022) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00677-0 · Cited by 172 · see citing works
Recent Advancement in mRNA Vaccine Development and Applications
Fayez, N. A., Nassar, M. S., Alshehri, A. A., Alnefaie, M. K., Almughem, F. A., Alshehri, B. Y., Alawad, A. O., & Tawfik, E. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071972 · Cited by 177 · see citing works
mRNA cancer vaccines: Advances, trends and challenges
He, Q., Gao, H., Tan, D., Zhang, H., & Wang, J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.03.011 · Cited by 167 · see citing works
“The ability of triplet mRNAs encoding IL-23, IL-36, and OX40L to improve the survival rate of MC38-S tumor-bearing mice was significantly stronger than that of the corresponding protein treatments 78 .”
InfluentialJain, S., Venkataraman, A. K., Wechsler, M. E., & Peppas, N. A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114000 · Cited by 163 · see citing works
Leveraging mRNA Sequences and Nanoparticles to Deliver SARS‐CoV‐2 Antigens In Vivo
Zeng, C., Hou, X., Yan, J., Zhang, C., Li, W., Zhao, W., Du, S., & Dong, Y. (2020) · Advanced Materials · doi:10.1002/adma.202004452 · Cited by 152 · see citing works
Aliprantis, A. O., Shaw, C. A., Griffin, P., Farinola, N., Railkar, R. A., Cao, X., Liu, W., Sachs, J. R., Swenson, C. J., Lee, H., et al. (2021) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2020.1829899 · Cited by 149 · see citing works
“mRNA vaccine technology has the potential to offer rapid antigen design and scalable production.(27,28) The nucleic acid approach eliminates the need to produce and purify proteins, a process which can be costly or challenging for unstable antigens.”
BackgroundThe use of RNA-based treatments in the field of cancer immunotherapy
Chehelgerdi, M., & Chehelgerdi, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01807-w · Cited by 146 · see citing works
Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics
Tan, X., Letendre, J. H., Collins, J. J., & Wong, W. W. (2021) · Cell · doi:10.1016/j.cell.2021.01.017 · Cited by 133 · see citing works
“Synthetic biology and biochemical approaches have been used to increase the intracellular stability of vaccine RNAs, reduce cytotoxicity, and enhance protein production (Jackson et al., 2020b; Pardi et al., 2020; Kowalski et al., 2019).”
MethodKowalzik, F., Schreiner, D., Jensen, C., Teschner, D., Gehring, S., & Zepp, F. (2021) · Vaccines · doi:10.3390/vaccines9040390 · Cited by 127 · see citing works
Next-Generation TB Vaccines: Progress, Challenges, and Prospects
Li, Z., Ye, Z., Li, L., Yang, L., & Gong, W. (2023) · Vaccines · doi:10.3390/vaccines11081304 · Cited by 121 · see citing works
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Chivukula, S., Plitnik, T., Tibbitts, T., Karve, S., Dias, A., Zhang, D., Goldman, R., Gopani, H., Khanmohammed, A., Sarode, A., et al. (2021) · npj Vaccines · doi:10.1038/s41541-021-00420-6 · Cited by 117 · see citing works
Development of mRNA Vaccines: Scientific and Regulatory Issues
Knezevic, I., Liu, M. A., Peden, K., Zhou, T., & Kang, H.-N. (2021) · Vaccines · doi:10.3390/vaccines9020081 · Cited by 114 · see citing works
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
From COVID-19 to Cancer mRNA Vaccines: Moving From Bench to Clinic in the Vaccine Landscape
Chakraborty, C., Sharma, A. R., Bhattacharya, M., & Lee, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.679344 · Cited by 111 · see citing works
A Review of Pseudorabies Virus Variants: Genomics, Vaccination, Transmission, and Zoonotic Potential
Bo, Z., & Li, X. (2022) · Viruses · doi:10.3390/v14051003 · Cited by 109 · see citing works
“A messenger RNA (mRNA)-based vaccine that encodes the immunogenetic antigen of pathogens provides a new vaccine developing platform for multiple viruses [49,50].”
BackgroundAdvances in mRNA non-viral delivery approaches
Ibba, M. L., Ciccone, G., Esposito, C. L., Catuogno, S., & Giangrande, P. H. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113930 · Cited by 107 · see citing works
Ye, Z., Chen, J., Zhao, X., Li, Y., Harmon, J., Huang, C., Chen, J., & Xu, Q. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c01532 · Cited by 110 · see citing works
Xu, S., Xu, Y., Solek, N. C., Chen, J., Gong, F., Varley, A., Golubovic, A., Pan, A., Dong, S., Zheng, G., et al. (2024) · Advanced Materials · doi:10.1002/adma.202400307 · Cited by 105 · see citing works
Current Developments and Challenges of mRNA Vaccines
Chen, J., Chen, J., & Xu, Q. (2022) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-110220-031722 · Cited by 106 · see citing works
Nanocarrier vaccines for SARS-CoV-2
Machhi, J., Shahjin, F., Das, S., Patel, M., Abdelmoaty, M. M., Cohen, J. D., Singh, P., Baldi, A., Bajwa, N., Kumar, R., et al. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.01.002 · Cited by 80 · see citing works
“mRNA is labile and prone to degradation primarily from nuclease activity within the cells; hence, efficient protection of the mRNA is critical during administration [285].”
Current and future nanoparticle vaccines for COVID-19
Vu, M. N., Kelly, H. G., Kent, S. J., & Wheatley, A. K. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103699 · Cited by 97 · see citing works
“…minimise opsonization in vivo and various helper lipids and cholesterol to support particle formation. mRNA-LNPs are fully synthetic and manufactured without the requirement of living cells, allowing rapid production of vaccines at scale within weeks after the availability of a viral genome [20].”
Zhang, C., Ma, Y., Zhang, J., Kuo, J. C., Zhang, Z., Xie, H., Zhu, J., & Liu, T. (2022) · Molecules · doi:10.3390/molecules27061943 · Cited by 93 · see citing works
“In addition, the expression of target antigen after translation is much faster than other platforms [256,289,290].”
BackgroundNucleic Acid Vaccines for COVID-19: A Paradigm Shift in the Vaccine Development Arena
Chavda, V. P., Hossain, M. M. M., Beladiya, J., & Apostolopoulos, V. (2021) · Biologics · doi:10.3390/biologics1030020 · Cited by 92 · see citing works
Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine
Huang, X., Zhang, G., Tang, T., Gao, X., & Liang, T. (2022) · Military Medical Research · doi:10.1186/s40779-022-00416-w · Cited by 95 · see citing works
“mRNA can be produced in vitro using a DNA template, ribonucleotide triphosphates, and recombinant enzymes [118, 119].”
BackgroundSARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?
Chakraborty, S., Mallajosyula, V. V. A., Tato, C. M., Tan, G. S., & Wang, T. T. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.01.014 · Cited by 87 · see citing works
Ripoll, M., Bernard, M., Vaure, C., Bazin, E., Commandeur, S., Perkov, V., Lemdani, K., Nicolaï, M., Bonifassi, P., Kichler, A., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121570 · Cited by 85 · see citing works
Zheng, B., Peng, W., Guo, M., Huang, M., Gu, Y., Wang, T., Ni, G., & Ming, D. (2021) · Chemical Engineering Journal · doi:10.1016/j.cej.2021.129392 · Cited by 83 · see citing works
“strict cold chain distribution and cryopreservation.[19] For recombinant protein vaccines represented by the receptor binding domain (RBD)”
Clinical development and approval of COVID-19 vaccines
Kalinke, U., Barouch, D. H., Rizzi, R., Lagkadinou, E., Türeci, Ö., Pather, S., & Neels, P. (2022) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2042257 · Cited by 82 · see citing works
“References:[12], [20], [29], [35], [36], [50], [53], [54], [59], [61-63].”
BackgroundA comprehensive comparison of DNA and RNA vaccines
Wang, C., & Yuan, F. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115340 · Cited by 87 · 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 production of mRNA vaccines is technically simple, fast, cost-effective, cell- and animal-material free, and easy to adapt [3] mRNA vaccines can be produced from linearized plasmid DNA templates or from polymerase chain reaction-based templates by in vitro transcription using phage RNA polymerases such as T7, T3,…”
BackgroundiCodon customizes gene expression based on the codon composition
Diez, M., Medina-Muñoz, S. G., Castellano, L. A., Pescador, G. D. S., Wu, Q., & Bazzini, A. (2022) · Scientific Reports · doi:10.1038/s41598-022-15526-7 · Cited by 74 · see citing works
Influenza Vaccination to Reduce Cardiovascular Morbidity and Mortality in Patients With COVID-19
Behrouzi, B., Campoverde, M. V. A., Liang, K., Talbot, H. K., Bogoch, I. I., McGeer, A., Fröbert, O., Loeb, M. B., Vardeny, O., Solomon, S. D., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.08.028 · Cited by 74 · see citing works
“Although this technology is reported to allow for faster production, it has never led to a licensed vaccine for sale (59).”
BackgroundLipid Nanoparticles as Promising Carriers for mRNA Vaccines for Viral Lung Infections
Asr, M. H., Dayani, F., Segherloo, F. S., Kamedi, A., Neill, A. O., MacLoughlin, R. J., & Doroudian, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041127 · Cited by 73 · see citing works
“including the prevention of infectious diseases; this is a research area that is currently under intense development [10,28].”
BackgroundThe mRNA Vaccine Revolution: COVID-19 Has Launched the Future of Vaccinology
Ye, Z., Harmon, J., Ni, W., Li, Y., Wich, D., & Xu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.2c12584 · Cited by 71 · see citing works
Influenza and Universal Vaccine Research in China
Li, J., Zhang, Y., Zhang, X., & Liu, L. (2022) · Viruses · doi:10.3390/v15010116 · Cited by 74 · see citing works
“mRNA vaccines are produced by introducing mRNA containing encoded antigenic proteins into the body, which are transcribed and translated to produce the corresponding antigenic proteins and induce a specific immune response [98].”
BackgroundmRNA 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
Recent Developments in Vaccine Design: From Live Vaccines to Recombinant Toxin Vaccines
Gupta, S., & Pellett, S. (2023) · Toxins · doi:10.3390/toxins15090563 · Cited by 70 · see citing works
Genito, C. J., Batty, C. J., Bachelder, E. M., & Ainslie, K. M. (2020) · Advanced NanoBiomed Research · doi:10.1002/anbr.202000041 · Cited by 65 · see citing works
“45 Polymeric encapsulation or complexation has been used to deliver mRNA and other nucleic acid vaccines, 46 but complexing it to cationic and ionizable lipids is much more common.”
Hameed, S. A., Paul, S., Dellosa, G. K. Y., Jaraquemada, D., & Bello, M. B. (2022) · npj Vaccines · doi:10.1038/s41541-022-00485-x · Cited by 64 · see citing works
Kavanagh, M. M., Gostin, L. O., & Sunder, M. (2021) · JAMA · doi:10.1001/jama.2021.10823 · Cited by 63 · see citing works
Therapeutic cancer vaccines revamping: technology advancements and pitfalls
Antonarelli, G., Corti, C., Tarantino, P., Ascione, L., Cortés, J., Romero, P. J., Mittendorf, E., Disis, M. L., & Curigliano, G. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.08.2153 · Cited by 63 · see citing works
“A key aspect of CV development efforts is the capacity of making early and objective treatment choices in order to select ideal candidates, a specific platform, eventual combinatorial agents, and vaccination schedules.(159) For RNA-based CVs, different aspects still need to be thoroughly assessed to boost their effica…”
Fast-track development of vaccines for SARS-CoV-2: The shots that saved the world
Chavda, V. P., Yao, Q., Vora, L. K., Apostolopoulos, V., Patel, C. A., Bezbaruah, R., Patel, A., & Chen, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.961198 · Cited by 62 · see citing works
Recent advances in immunotherapies against infectious diseases
Ramamurthy, D., Nundalall, T., Cingo, S., Mungra, N., Karaan, M., Naran, K., & Barth, S. (2020) · Immunotherapy Advances · doi:10.1093/immadv/ltaa007 · Cited by 63 · see citing works
“There are currently no licensed RNA vaccines for human application, however, clinical trials are currently underway to develop mRNA vaccines expressing the pre-membrane (prM) and envelope (E) proteins of the Zika virus (ZIKV) (NCT04064905; NCT03014089) [11, 12].”
BackgroundCodonBERT large language model for mRNA vaccinesPreprint
Li, S., Moayedpour, S., Li, R., Bailey, M., Riahi, S., Kogler-Anele, L., Miladi, M., Miner, J. C., Pertuy, F., Zheng, D., et al. (2024) · Genome Research · doi:10.1101/gr.278870.123 · Cited by 64 · see citing works
COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform
Ashraf, M. U., Kim, Y., Kumar, S., Seo, D., Ashraf, M., & Bae, Y. (2021) · Vaccines · doi:10.3390/vaccines9020171 · Cited by 61 · see citing works
Knowledge transfer for large-scale vaccine manufacturing
Price, W. N., Rai, A. K., & Minssen, T. (2020) · Science · doi:10.1126/science.abc9588 · Cited by 60 · see citing works
Antigenic characterization of influenza and SARS-CoV-2 viruses
Wang, Y., Tang, C. Y., & Wan, X. (2021) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-021-03806-6 · Cited by 60 · see citing works
“As with all vaccine platforms, mRNA vaccines also present challenges that will need to be addressed moving forward which include thermal instability at elevated temperatures, allergic reactions to LNPs, and the unknowns of long-term properties in humans including the effects of repeated administration [417, 456].”
BackgroundSupabphol, S., Li, L., Goedegebuure, S. P., & Gillanders, W. E. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1896702 · Cited by 59 · see citing works
DeFrancesco, L. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0697-7 · Cited by 56 · see citing works
COVID-19: Insights into Potential Vaccines
Loo, K.-Y., Letchumanan, V., Ser, H., Teoh, S. L., Law, J. W., Tan, L. T., Mutalib, N. A., Chan, K., & Lee, L. (2021) · Microorganisms · doi:10.3390/microorganisms9030605 · Cited by 56 · see citing works
COVID-19 vaccine platforms: Delivering on a promise?
Verdecia, M. A., Kokai‐Kun, J. F., Kibbey, M., Acharya, S., Venema, J., & Atouf, F. (2021) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2021.1911204 · Cited by 55 · see citing works
“Messenger RNA is a noninfectious, non-integrating technology with no potential to cause infections or insertional mutagenesis.(176) mRNA is also easily degraded, and its halflife can be regulated through modifications to the template or delivery method.”
BackgroundCurrent Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development
Kim, D.-K., Lai, C., Cha, I., & Jung, J. U. (2024) · Viruses · doi:10.3390/v16010128 · Cited by 56 · see citing works
Analyzing immune responses to varied mRNA and protein vaccine sequences
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“…modi fi cation by pseudouridine have shown the potential to overcome these limitations 4,5 . mRNA does not integrate into the host genome, eliminating the need for insertional mutagenesis 6 ; it can be manufactured in a cell-free manner, allowing rapid, scalable, and cost-effective production 7 .”
Barazzone, G. C., Teixeira, A. F., Azevedo, B. O. P., Damiano, D. K., Oliveira, M. P., Nascimento, A. L. T. O., & Lopes, A. P. Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.760291 · Cited by 52 · see citing works
Neonatal herpes simplex virus infection: From the maternal infection to the child outcome
Rose, D. U. D., Bompard, S., Maddaloni, C., Bersani, I., Martini, L., Santisi, A., Longo, D., Ronchetti, M. P., Dotta, A., & Auriti, C. (2023) · Journal of Medical Virology · doi:10.1002/jmv.29024 · Cited by 51 · see citing works
Current Vaccine Platforms in Enhancing T-Cell Response
Ura, T., Takeuchi, M., Kawagoe, T., Mizuki, N., Okuda, K., & Shimada, M. (2022) · Vaccines · doi:10.3390/vaccines10081367 · Cited by 50 · see citing works
mRNA vaccines in the prevention and treatment of diseases
Gu, Y., Duan, J., Yang, N., Yang, Y., & Zhao, X. (2022) · MedComm · doi:10.1002/mco2.167 · Cited by 51 · see citing works
Lin, W., Shen, C., Li, M., Ma, S., Liu, C., Huang, J., Ren, Z., Yang, Y., Zhao, M., Xie, Q., et al. (2024) · Advanced Science · doi:10.1002/advs.202408608 · Cited by 47 · see citing works
mRNA Vaccines: Why Is the Biology of Retroposition Ignored?
Domazet‐Lošo, T. (2022) · Genes · doi:10.3390/genes13050719 · Cited by 44 · see citing works
“It was often suggested that the main advantage of mRNA-based vaccines, compared to the more conventional approaches is the possibility of their rapid development and largescale deployment [6,7], which are both desirable properties in pandemic situations.”
BackgroundSchmid, P., & Betsch, C. (2022) · Science Communication · doi:10.1177/10755470221129608 · Cited by 44 · see citing works
“In addition, mRNA vaccines are considered beneficial over conventional vaccines because, among other things, these new types of vaccines allow rapid manufacturing, which is essential for a successful pandemic response (Jackson et al., 2020; Pardi et al., 2018).”
BackgroundShaw, C. A., August, A., Bart, S., Jackson-Booth, P.-G., Knightly, C., Brasel, T., Weaver, S. C., Zhou, H., & Panther, L. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.04.064 · Cited by 46 · see citing works
- Authors
- Jackson, N. A. C., Kester, K. E., Casimiro, D., Gurunathan, S., & DeRosa, F.
- Affiliations
- Coalition for Epidemic Preparedness Innovations (US)
- Sanofi (United States) (US)
- Translate Bio (United States) (US)
- Corresponding author
- Jackson, Nicholas A. C.
- Venue
- npj Vaccines
- Published
- 2020-02-04
- Volume
- 5
- Issue
- 1
- Pages
- 11-11
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC7000814
- OpenAlex
- W3004539389
- Cited by
- 498
- References
- 68
- Citations by year
- 2026: 39 · 2025: 54 · 2024: 70 · 2023: 76 · 2022: 110 · 2021: 121 · 2020: 28
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- 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 › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA vaccines, infectious disease prevention, mRNA delivery, vaccine production, translation efficiency, vaccine development, biotechnology industry, pharmaceutical industry
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