Cited by 110RNA Interference and Gene DeliveryRNA and protein synthesis mechanismsRNA Research and Splicing

An overview of rational design of mRNA-based therapeutics and vaccines

To, Kenneth K.W., Cho, William C.S.·2021·Expert Opinion on Drug Discovery

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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Crossref · 10.1080/17460441.2021.1935859

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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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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
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

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