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mRNA vaccines — a new era in vaccinology
Open accessAbstract
mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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“mRNA production and lipid nanoparticle formulation are fast and highly scalable, which renders this technology suitable for the rapid development and supply of vaccines during pandemic scenarios 11,12 .”
From BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans (2021) · cites this paper as [11]
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
“samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions6,44.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [44]
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 [2]
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 technique can be easily scaled requiring minimum platform changes during mRNA formulation and production (Pardi et al. 2018).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Pardi et al. 2018
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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 [10]
The cited source says what the claim attributes to it.
In the citing paper
“The mRNA also does not interact with the genome and only the parts directly required for the encoded protein expression are present in this basic genetic construct (Pardi et al. 2018).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Pardi et al. 2018
In the citing paper
“Both BNT162b2 and mRNA-1273, as well as the adenoviral-vectored vaccine ChAdOx1 nCoV-19, have been shown to induce type I interferon, thus potentially inducing pathogen-agnostic protection75–77.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [75]
In the citing paper
“Non-replicating mRNA vaccines deliver exclusively genetic information coding for the target antigen, thus containing the 5′-cap, 5′ untranslated region (UTR), 3′ UTR, and 3′-poly(A) tail regions.108”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [108]
In the citing paper
“Furthermore, the upscaling of cell-free vaccine production is relatively straightforward, thereby providing a cutting-edge tool for rapid response in epidemics and pandemics.4, 5, 6, 7”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [5]
In the citing paper
“Unlike some viral vaccines, mRNA does not integrate into the genome, obviating concerns about insertional mutagenesis5.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [5]
In the citing paper
“The use of modified nucleosides, particularly modified uridine, prevents recognition by pattern recognition receptors, enabling sufficient levels of translation to produce prophylactic amounts of protein5.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [5]
In the citing paper
“although it has been employed for various therapeutic targets, its use as a source of antigen in vaccination approaches is by far the most popular [2]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [2]
In the citing paper
“mRNA has shown therapeutic potential in a range of applications, including viral vaccines, protein replacement therapies, cancer immunotherapies, cellular reprogramming and genome editing2,4,7–17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“mRNA normally contains five structural elements, that is, a 5′ cap, a 3′ poly(A) tail, a protein-coding sequence and 5′ and 3′ untranslated regions (UTRs)2,4,7,13.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“mRNA is susceptible to degradation and, thus, formulation buffers should be free of any ribonuclease contaminations2,4.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“These elements can be engineered to improve the stability and translational efficiency of mRNA2,4,7,13.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Chromatographic purification can remove double-stranded RNA, an analogue of viral genome, in IVT mRNA preparations, diminishing immune activation and increasing translational efficiency2,4,7,183.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Chemical modifications of specific IVT mRNA nucleotides, such as pseudouridine (ψ) and N1-methylpseudouridine (m1ψ), can reduce innate immune sensing of exogenous mRNA translation2,4,7,182.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Many other lipid nanoparticle–mRNA formulations are in clinical trials for the treatment of infectious diseases, cancer and genetic disorders2,4,8,12–14 (Tables 1,2).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“These features make lipid nanoparticle–mRNA formulations a flexible and on-demand vaccine platform to rapidly respond to emerging infectious pathogens4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“To address these concerns, the engineering of mRNA molecules (Box 1) and the design of lipid nanoparticles have been optimized2,4,7–17, which has contributed to the rapid development and clinical assessment15,17 of the two COVID-19 mRNA vaccines, mRNA-1273 (NCT04470427)19,20 and BNT162b2 (NCT04368728)21.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Since then, lipid nanoparticle–mRNA formulations have emerged as a potent alternative to conventional vaccine platforms, owing to their unique features4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Moreover, mRNA-based cellular reprogramming, tissue regeneration and genome editing have shown therapeutic potential in preclinical studies2,4,8,12–14.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“First, mRNA is a non-infective and non-integrating agent with the ability to encode a broad range of antigens4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Finally, GMP-grade lipid nanoparticle-mRNA vaccines can be manufactured for specific antigens in a short period of time, compared with other vaccine platforms, such as recombinant proteins and inactivated vaccines2,4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Neoantigens are often different between individual patients, allowing the development of personalized vaccines4,11.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“Neoantigens, generated by somatic mutations in cancer cells, are usually tumour-specific and have high immunogenicity4,11.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“The sequences of these elements regulate translation initiation, translation termination and post-transcriptional modification of mRNA molecules2,4.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“To achieve effective translation, mRNA requires five structural elements, including the 5′ cap, 3′ poly(A) tail, protein-coding sequence and 5′ and 3′ untranslated regions (UTRs)2,4.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [4]
In the citing paper
“the application of RNA vaccines has been limited by their lack of stability and requirement for a cold chain”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [131]
In the citing paper
“RNA vaccines, for example, have exhibited encouraging results in both infection therapy and cancer immunotherapy.[6, 7, 11–15]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [12]
In the citing paper
“mRNA functions as the bridge between DNA and proteins in eukaryotic cells.[8, 12, 119]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [12]
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Flagged first, then by citations
1 of the 218 references couldn’t be matched to a known paper.
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Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076
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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
Metadata
- Authors
- Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- Duke University (US)
- Corresponding author
- Weissman, Drew
- Venue
- Nature Reviews Drug Discovery
- Published
- 2018-01-12
- Volume
- 17
- Issue
- 4
- Pages
- 261-279
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC5906799
- OpenAlex
- W2782708334
- Cited by
- 4,667
- References
- 218
- Citations by year
- 2026: 640 · 2025: 683 · 2024: 630 · 2023: 662 · 2022: 801 · 2021: 808 · 2020: 303 · 2019: 90 · 2018: 49
- FWCI
- 30.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bill and Melinda Gates Foundation (OPP1066832, OPP1033102)
- National Institutes of Health (AI084860, AI-100645)
- Defense Advanced Research Projects Agency (HR0011‐17‐2‐0069)
- Advanced Research Projects Agency
- National Institute of Allergy and Infectious Diseases (AI-100645, UM1AI100645, R01-AI084860, R01AI050484, R01AI124429, AI124429, U01AI067854, R01AI090788)
- 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
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- mRNA vaccines, mRNA stability, mRNA delivery, vaccine platforms, cancer vaccines, infectious disease vaccines, vaccine development
- MeSH terms
- Vaccinology, Animals, Humans, Neoplasms, RNA, Messenger, Vaccines
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