An overview of rational design of mRNA-based therapeutics and vaccines
Abstract
Introduction Messenger RNA (mRNA)-based therapeutics and vaccines have emerged as a disruptive new drug class for various applications, including regenerative medicine, cancer treatment, and prophylactic and therapeutic vaccinations.Areas covered This review provides an update about the rational structure-based design of various formats of mRNA-based therapeutics. The authors discuss the recent advances in the mRNA modifications that have been used to enhance stability, promote translation efficiency and regulate immunogenicity for specific applications.Expert opinion Extensive research efforts have been made to optimize mRNA constructs and preparation procedures to unleash the full potential of mRNA-based therapeutics and vaccines. Sequence optimization (untranslated region and codon usage), chemical engineering of nucleotides and modified 5ʹcap, and optimization of in vitro transcription and mRNA purification protocols have overcome the major obstacles (instability, delivery, immunogenicity and safety) hindering the clinical applications of mRNA therapeutics and vaccines. The optimized design parameters should not be applied as default to different biological systems, but rather individually optimized for each mRNA sequence and intended application. Further advancement in the mRNA design and delivery technologies for achieving cell type- and organ site-specificity will broaden the scope and usefulness of this new class of drugs.
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In mammalian cells, actively translated mRNAs generally contain 100-250 adenosine residues.
“In mammalian cells, actively translated mRNAs generally contain 100–250 adenosine residues.117,150”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [117]
An mRNA of cap 0 is likely to be recognized as exogenous RNA by the host, which could stimulate the innate immune response and trigger inflammatory responses.
“however, an mRNA of cap 0 is likely to be recognized as exogenous RNA by the host, which could stimulate the innate immune response of the host and ultimately trigger inflammatory responses.117”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [117]
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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
- Authors
- To, K. K. W., & Cho, W. C. S.
- Affiliations
- Chinese University of Hong Kong (HK)
- Queen Elizabeth Hospital (CN)
- Corresponding author
- To, Kenneth K.W.
- Cho, William C.S.
- Venue
- Expert Opinion on Drug Discovery
- Publisher
- Informa UK Limited
- Published
- 2021-07-19
- Volume
- 16
- Issue
- 11
- Pages
- 1307-1317
- ISSN
- 1746-0441 (ISSN-L)
- 1746-045X
- OpenAlex
- W3164412373
- Cited by
- 110
- References
- 115
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 29 · 2023: 22 · 2022: 11 · 2021: 2 · 2020: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- mRNA therapeutics, mRNA vaccines, rational design, mRNA modification, 5' cap, codon optimization, untranslated regions, in vitro transcription, mRNA stability, immunogenicity, mRNA delivery
- MeSH terms
- Pharmaceutical Preparations, Proteins, RNA, Messenger, Vaccines, Drug Delivery Systems
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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