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Engineering circular RNA for enhanced protein production
Nature Biotechnology ( IF 46.9 ) Pub Date : 2022-07-18 , DOI: 10.1038/s41587-022-01393-0
Robert Chen 1 , Sean K Wang 1, 2 , Julia A Belk 3 , Laura Amaya 1 , Zhijian Li 4 , Angel Cardenas 1 , Brian T Abe 1 , Chun-Kan Chen 1 , Paul A Wender 4, 5 , Howard Y Chang 1, 6
Affiliation  

Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing. Synthetic circRNAs and some endogenous circRNAs can encode proteins, raising the promise of circRNA as a platform for gene expression. In this study, we developed a systematic approach for rapid assembly and testing of features that affect protein production from synthetic circRNAs. To maximize circRNA translation, we optimized five elements: vector topology, 5′ and 3′ untranslated regions, internal ribosome entry sites and synthetic aptamers recruiting translation initiation machinery. Together, these design principles improve circRNA protein yields by several hundred-fold, provide increased translation over messenger RNA in vitro, provide more durable translation in vivo and are generalizable across multiple transgenes.



中文翻译:

用于增强蛋白质生产的工程环状 RNA

环状 RNA (circRNA) 是真核细胞中稳定且普遍存在的 RNA,由反向剪接产生。合成的 circRNA 和一些内源性 circRNA 可以编码蛋白质,提高了 circRNA 作为基因表达平台的前景。在这项研究中,我们开发了一种系统的方法来快速组装和测试影响合成 circRNA 蛋白质生产的特征。为了最大化 circRNA 翻译,我们优化了五个要素:矢量拓扑结构、5' 和 3' 非翻译区、内部核糖体进入位点和合成适体招募翻译起始机制。总之,这些设计原则将 circRNA 蛋白产量提高了数百倍,在体外提供了比信使 RNA 更高的翻译,在体内提供了更持久的翻译,并且可以在多个转基因中推广。

更新日期:2022-07-19
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