Nikita Vostrosablin, Shuhui Lim, Pooja Gopal, Kveta Brazdilova, Sushmita Parajuli, Xiaona Wei, Anna Gromek, David Prihoda, Martin Spale, Anja Muzdalo, Jamie Greig, Constance Yeo, Joanna Wardyn, Petr Mejzlik, Brian Henry, Anthony W Partridge, Danny A Bitton
{"title":"mRNAid, an open-source platform for therapeutic mRNA design and optimization strategies.","authors":"Nikita Vostrosablin, Shuhui Lim, Pooja Gopal, Kveta Brazdilova, Sushmita Parajuli, Xiaona Wei, Anna Gromek, David Prihoda, Martin Spale, Anja Muzdalo, Jamie Greig, Constance Yeo, Joanna Wardyn, Petr Mejzlik, Brian Henry, Anthony W Partridge, Danny A Bitton","doi":"10.1093/nargab/lqae028","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":33994,"journal":{"name":"NAR Genomics and Bioinformatics","volume":"6 1","pages":"lqae028"},"PeriodicalIF":4.0000,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935487/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NAR Genomics and Bioinformatics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/nargab/lqae028","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
