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微RNA响应开关的合理设计,用于哺乳动物细胞中的可编程翻译控制

Hui Ning¹, Gan Liu², Lei Li¹

¹MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing, 100084, China.

Nature communications

|November 8, 2023

概括

研究人员开发了一种可编程RNA系统 (PROMITAR),用于精确控制翻译. 这种合成生物学工具能够在特定细胞中进行上调和下调基因表达,并具有潜在的治疗用途.

科学领域:

合成生物学合成生物学
在RNA疗法方面.
分子工程分子工程分子工程

背景情况:

目前的RNA翻译调制依赖于复杂的系统,如RNA结合蛋白 (RBPs) 和微RNA (miRNAs).
转化循环RNAs (circRNAs) 为线性信使RNAs (mRNAs) 提供了替代方案,但缺乏可编程控制.
需要简单的策略来为高级合成生物学应用程序编程circRNA翻译.

研究的目的:

设计一个可编程的平台,用于miRNA-响应的内部核糖体进入点 (IRES) 中介的翻译控制.
为了在单个RNA结构中实现翻译的上调和下调.
为了证明这个平台在构建逻辑门和细胞类型分类器中的实用性.

主要方法:

一个可编程miRNA响应IRES翻译激活和抑制 (PROMITAR) 平台的合理设计.
使用PROMITAR平台的circRNAs的工程.
构建和测试逻辑门和细胞类型分类器circRNAs用于哺乳动物细胞识别.
在工程 circRNA 中编码细胞毒性蛋白质,用于向杀死癌细胞.

主要成果:

成功开发了PROMITAR平台,用于在circRNA中基于miRNA的双向翻译控制.
证明了功能逻辑门和细胞类型分类器circRNAs的构建.
使用工程 circRNAs 成功识别了特定的哺乳动物细胞类型.
通过用工程 circRNAs 向杀死癌细胞来治疗应用的概念验证.

结论:

PROMITAR平台提供了一种新的可编程策略,用于控制circRNA的翻译.
工程 circRNAs 可以作为复杂的生物逻辑门和细胞类型分类器.
这个平台具有很大的潜力,可以推进RNA合成生物学和开发向的RNA疗法.

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