Design principles and applications of synthetic self-replicating RNAs.

IF 6.4 2区 生物学 Q1 CELL BIOLOGY Wiley Interdisciplinary Reviews: RNA Pub Date : 2023-11-01 Epub Date: 2023-06-01 DOI:10.1002/wrna.1803
Alexander Wagner, Hannes Mutschler
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Abstract

With the advent of ever more sophisticated methods for the in vitro synthesis and the in vivo delivery of RNAs, synthetic mRNAs have gained substantial interest both for medical applications, as well as for biotechnology. However, in most biological systems exogeneous mRNAs possess only a limited half-life, especially in fast dividing cells. In contrast, viral RNAs can extend their lifetime by actively replicating inside their host. As such they may serve as scaffolds for the design of synthetic self-replicating RNAs (srRNA), which can be used to increase both the half-life and intracellular concentration of coding RNAs. Synthetic srRNAs may be used to enhance recombinant protein expression or induce the reprogramming of differentiated cells into pluripotent stem cells but also to create cell-free systems for research based on experimental evolution. In this article, we discuss the applications and design principles of srRNAs used for cellular reprogramming, mRNA-based vaccines and tools for synthetic biology. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.

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合成自我复制rna的设计原理和应用。
随着越来越复杂的rna体外合成和体内递送方法的出现,合成mrna在医学应用和生物技术方面都获得了极大的兴趣。然而,在大多数生物系统中,外源性mrna只有有限的半衰期,特别是在快速分裂的细胞中。相比之下,病毒rna可以通过在宿主体内积极复制来延长它们的寿命。因此,它们可以作为设计合成自复制rna (srRNA)的支架,可用于增加编码rna的半衰期和细胞内浓度。合成srRNAs可用于增强重组蛋白表达或诱导分化细胞重编程为多能干细胞,也可用于基于实验进化的研究创建无细胞系统。在本文中,我们讨论了srrna用于细胞重编程、基于mrna的疫苗和合成生物学工具的应用和设计原则。本文分类为:疾病与发展中的RNA;疾病与发展中的RNA;疾病与发展中的RNA; bb1发育中的RNA; RNA进化与基因组学;bb2 RNA与核糖核蛋白进化。
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来源期刊
CiteScore
14.80
自引率
4.10%
发文量
67
审稿时长
6-12 weeks
期刊介绍: WIREs RNA aims to provide comprehensive, up-to-date, and coherent coverage of this interesting and growing field, providing a framework for both RNA experts and interdisciplinary researchers to not only gain perspective in areas of RNA biology, but to generate new insights and applications as well. Major topics to be covered are: RNA Structure and Dynamics; RNA Evolution and Genomics; RNA-Based Catalysis; RNA Interactions with Proteins and Other Molecules; Translation; RNA Processing; RNA Export/Localization; RNA Turnover and Surveillance; Regulatory RNAs/RNAi/Riboswitches; RNA in Disease and Development; and RNA Methods.
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