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

N. Vostrosablin, S. Lim, P. Gopal, K. Brazdilova, S. Parajuli, X. Wei, A. Gromek, D. Prihoda, M. Spale, A. Muzdalo, J. Greig, C. Yeo, J. Wardyn, P. Mejzlik, B. Henry, AW. Partridge, DA. Bitton

. 2024 ; 6 (1) : lqae028. [pub] 20240312

Status neindexováno Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24005607

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.

Citace poskytuje Crossref.org

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