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Review
. 2024 Mar 7;42(7):1831-1840.
doi: 10.1016/j.vaccine.2023.07.024. Epub 2023 Jul 20.

Computational design of mRNA vaccines

Yoo-Ah Kim  1 , Kambiz Mousavi  1 , Amirali Yazdi  2 , Magda Zwierzyna  3 , Marco Cardinali  3 , Dillion Fox  4 , Thomas Peel  2 , Jeff Coller  5 , Kunal Aggarwal  1 , Giulietta Maruggi  6
Affiliations
Review

Computational design of mRNA vaccines

Yoo-Ah Kim et al. Vaccine. .

Abstract

mRNA technology has emerged as a successful vaccine platform that offered a swift response to the COVID-19 pandemic. Accumulating evidence shows that vaccine efficacy, thermostability, and other important properties, are largely impacted by intrinsic properties of the mRNA molecule, such as RNA sequence and structure, both of which can be optimized. Designing mRNA sequence for vaccines presents a combinatorial problem due to an extremely large selection space. For instance, due to the degeneracy of the genetic code, there are over 10632 possible mRNA sequences that could encode the spike protein, the COVID-19 vaccines' target. Moreover, designing different elements of the mRNA sequence simultaneously against multiple objectives such as translational efficiency, reduced reactogenicity, and improved stability requires an efficient and sophisticated optimization strategy. Recently, there has been a growing interest in utilizing computational tools to redesign mRNA sequences to improve vaccine characteristics and expedite discovery timelines. In this review, we explore important biophysical features of mRNA to be considered for vaccine design and discuss how computational approaches can be applied to rapidly design mRNA sequences with desirable characteristics.

Keywords: Optimization; Vaccines; mRNA sequence; mRNA structure.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeff Coller reports a relationship with Tevard Biosciences that includes: board membership, consulting or advisory, and equity or stocks. Kambiz Mousavi, Magda Zwierzyna, Yoo-Ah Kim, Amirali Yazdi & Giulietta Maruggi have patent pending to GSK. Funding: This work was sponsored by GlaxoSmithKline Biologicals SA. Conflict of interest Y-AK, KM, AY, MZ, MC, DF, TP, NW, KA and GM, are, or were at the time of the study employees of the GSK group of companies and may hold GSK shares and/or may be inventors on patents owned by GSK. JC is the Scientific Co-Founder of Tevard Biosciences and a member of its Scientific Advisory Board.

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