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

Autor:	Vostrosablin N; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Lim S; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Gopal P; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Brazdilova K; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic.; Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, 160 00, Czech Republic., Parajuli S; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Wei X; Bioinformatics, MSD Singapore, 138665, Singapore., Gromek A; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Prihoda D; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Spale M; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Muzdalo A; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Greig J; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Yeo C; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Wardyn J; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Mejzlik P; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic., Henry B; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Partridge AW; Quantitative Biosciences, MSD Singapore, 138665, Singapore., Bitton DA; Discovery Informatics, MSD Czech Republic s.r.o., Prague, 150 00, Czech Republic.
Jazyk:	angličtina
Zdroj:	NAR genomics and bioinformatics [NAR Genom Bioinform] 2024 Mar 12; Vol. 6 (1), pp. lqae028. Date of Electronic Publication: 2024 Mar 12 (Print Publication: 2024).
DOI:	10.1093/nargab/lqae028
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
Databáze:	MEDLINE
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