小柯机器人

美国斯坦福大学Howard Y. Chang研究团队开发出增强蛋白质产生的环状RNA。该项研究成果于2022年7月18日在线发表在《自然—生物技术》杂志上。

研究人员开发了一种系统的方法，用于快速组装和测试影响合成环状RNA（circRNA）蛋白生产的特征。为了最大限度地提高circRNA的翻译，研究人员优化了五个要素：载体拓扑结构、5′和3′非翻译区、内部核糖体进入位点和招募翻译启动机器的合成适配子。这些设计原则结合在一起，使circRNA的蛋白质产量提高了几百倍，在体外提供了比信使RNA更多的翻译，在体内提供了更持久的翻译，并可在多个转基因中通用。

据悉，circRNA是真核细胞中稳定而普遍的RNA，由反向拼接产生。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。

附：英文原文

Title: Engineering circular RNA for enhanced protein production

Author: Chen, Robert, Wang, Sean K., Belk, Julia A., Amaya, Laura, Li, Zhijian, Cardenas, Angel, Abe, Brian T., Chen, Chun-Kan, Wender, Paul A., Chang, Howard Y.

Issue&Volume: 2022-07-18

Abstract: 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.

DOI: 10.1038/s41587-022-01393-0

Source: https://www.nature.com/articles/s41587-022-01393-0

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex