von der Haar Tobias, Mulroney Thomas E, Hedayioglu Fabio, Kurusamy Sathishkumar, Rust Maria, Lilley Kathryn S, Thaventhiran James E, Willis Anne E, Smales C Mark
School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, United Kingdom.
MRC Toxicology Unit, Gleeson Building, University of Cambridge, Cambridge, United Kingdom.
Front Mol Biosci. 2023 Feb 8;10:1128067. doi: 10.3389/fmolb.2023.1128067. eCollection 2023.
transcribed, modified messenger RNAs (IVTmRNAs) have been used to vaccinate billions of individuals against the SARS-CoV-2 virus, and are currently being developed for many additional therapeutic applications. IVTmRNAs must be translated into proteins with therapeutic activity by the same cellular machinery that also translates native endogenous transcripts. However, different genesis pathways and routes of entry into target cells as well as the presence of modified nucleotides mean that the way in which IVTmRNAs engage with the translational machinery, and the efficiency with which they are being translated, differs from native mRNAs. This review summarises our current knowledge of commonalities and differences in translation between IVTmRNAs and cellular mRNAs, which is key for the development of future design strategies that can generate IVTmRNAs with improved activity in therapeutic applications.
转录修饰的信使核糖核酸（IVT mRNA）已被用于为数十亿人接种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒的疫苗，目前正被开发用于许多其他治疗应用。IVT mRNA必须通过与翻译天然内源性转录本相同的细胞机制翻译成具有治疗活性的蛋白质。然而，不同的生成途径、进入靶细胞的途径以及修饰核苷酸的存在意味着IVT mRNA与翻译机制的结合方式及其翻译效率与天然mRNA不同。本综述总结了我们目前对IVT mRNA和细胞mRNA在翻译方面的异同的认识，这对于开发未来的设计策略以产生在治疗应用中具有更高活性的IVT mRNA至关重要。
