mRNAid, an open-source platform for therapeutic mRNA design and optimization strategies

Author:

Vostrosablin Nikita1,Lim Shuhui2,Gopal Pooja2,Brazdilova Kveta13,Parajuli Sushmita1,Wei Xiaona4,Gromek Anna1,Prihoda David1,Spale Martin1,Muzdalo Anja1,Greig Jamie2,Yeo Constance2,Wardyn Joanna2,Mejzlik Petr1,Henry Brian2,Partridge Anthony W2,Bitton Danny A1ORCID

Affiliation:

1. Discovery Informatics, MSD Czech Republic s.r.o. , Prague , 150 00, Czech Republic

2. Quantitative Biosciences , MSD Singapore , 138665, Singapore

3. Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology , Prague , 160 00, Czech Republic

4. Bioinformatics , MSD Singapore , 138665, Singapore

Abstract

Abstract Recent COVID-19 vaccines unleashed the potential of mRNA-based therapeutics. A common bottleneck across mRNA-based therapeutic approaches is the rapid design of mRNA sequences that are translationally efficient, long-lived and non-immunogenic. Currently, an accessible software tool to aid in the design of such high-quality mRNA is lacking. Here, we present mRNAid, an open-source platform for therapeutic mRNA optimization, design and visualization that offers a variety of optimization strategies for sequence and structural features, allowing one to customize desired properties into their mRNA sequence. We experimentally demonstrate that transcripts optimized by mRNAid have characteristics comparable with commercially available sequences. To encompass additional aspects of mRNA design, we experimentally show that incorporation of certain uridine analogs and untranslated regions can further enhance stability, boost protein output and mitigate undesired immunogenicity effects. Finally, this study provides a roadmap for rational design of therapeutic mRNA transcripts.

Funder

Merck Sharp & Dohme

Merck & Co., Inc.

Publisher

Oxford University Press (OUP)

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