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Review
. 2022 Apr;45(4):245-262.
doi: 10.1007/s12272-022-01381-7. Epub 2022 Apr 15.

mRNA vaccines: the most recent clinical applications of synthetic mRNA

Suji Kwon  1 , Minseon Kwon  1 , Seongeun Im  1 , Kyuri Lee  2 , Hyukjin Lee  3
Affiliations
Review

mRNA vaccines: the most recent clinical applications of synthetic mRNA

Suji Kwon et al. Arch Pharm Res. 2022 Apr.

Abstract

Synthetic mRNA has been considered as an emerging biotherapeutic agent for the past decades. Recently, the SARS-CoV-2 pandemic has led to the first clinical use of synthetic mRNA. mRNA vaccines showed far surpassing influences on the public as compared to other vaccine platforms such as viral vector vaccines and recombinant protein vaccines. It allowed rapid development and production of vaccines that have never been achieved in history. Synthetic mRNA, called in vitro transcribed (IVT) mRNA, is the key component of mRNA vaccines. It has several advantages over conventional gene-expressing systems such as plasmid DNA and viral vectors. It can translate proteins in the cytoplasm by structurally resembling natural mRNA and exhibit various protein expression patterns depending on how it is engineered. Another advantage is that synthetic mRNA enables fast, scalable, and cost-effective production. Therefore, starting with the mRNA vaccine, synthetic mRNA is now in the spotlight as a promising new drug development agent. In this review, we will summarize the latest IVT mRNA technology such as new mRNA structures or large-scale production. In addition, the nature of the innate immunogenicity of IVT mRNA will be discussed along with its roles in the development of vaccines. Finally, the principles of the mRNA vaccine and the future direction of synthetic mRNA will be provided.

Keywords: In vitro transcribed (IVT) mRNA; mRNA vaccines.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Structure and functional component of linear mRNA. Schematic structure of linear mRNA and major functions of each component
Fig. 2
Fig. 2
Structure and functional components of self-amplifying mRNA and circular mRNA. A Schematic structure of self-amplifying mRNA. B Schematic structure of circular mRNA. (Some structures such as homology arms and spacers are omitted from this figure)
Fig. 3
Fig. 3
Preparation process of IVT mRNA. (1) cDNA encoding antigen inserted to DNA template. DNA template must include the sequence of the T7 promoter, 5′ UTR, and 3′ UTR. (2) T7 RNA polymerase synthesis IVT mRNA. Both 5′ cap and the poly A tail can be synthesized in two methods. (3) A purification process is required to remove unintended and immunogenic impurities
Fig. 4
Fig. 4
Mechanism of the mRNA vaccines. Upon the introduction of IVT mRNA into cells, various TLRs and PRRs recognize the presence of exogenous mRNA and trigger innate immune responses. IVT mRNA delivered in the cytoplasm of cells directly utilizes the host translation system to express target proteins. Expressed proteins are further processed by proteasomes and moved to the cellular membrane by MHC class I
See this image and copyright information in PMC

References

    1. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413(6857):732–738. doi: 10.1038/35099560. - DOI - PubMed
    1. Baden LR, El Sahly HM, Essink B, Kotloff K, Sharon Frey MD, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416. doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
    1. Baiersdörfer M, Boros G, Muramatsu H, Mahiny A, Vlatkovic I, Sahin U, Karikó K. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol Ther Nucleic Acids. 2019;15:26–35. doi: 10.1016/j.omtn.2019.02.018. - DOI - PMC - PubMed
    1. Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, Chew A, Zhao Y, Levine BL, Albelda SM, Kalos M, June CH. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2(2):112–120. doi: 10.1158/2326-6066.CIR-13-0170. - DOI - PMC - PubMed
    1. Beck JD, Reidenbach D, Salomon N, Sahin U, Türeci Ö, Vormehr M, Kranz LM. mRNA therapeutics in cancer immunotherapy. Mol Cancer. 2021;20(1):69. doi: 10.1186/s12943-021-01348-0. - DOI - PMC - PubMed