One of the most prevalent forms of post-transcriptional RNA modification is the conversion of adenosine-to-inosine (A-to-I), mediated by adenosine deaminase acting on RNA (ADAR) enzymes. The advent of the CRISPR/Cas systems inspires researchers to work actively in the engineering of programmable RNA-guided machines for basic research and biomedical applications. In this regard, CIRTS (CRISPR-Cas-Inspired RNA Targeting System), RESCUE (RNA Editing for Specific C to U Exchange), RESTORE (Recruiting Endogenous ADAR to Specific Transcripts for Oligonucleotide-mediated RNA Editing), and LEAPER (Leveraging Endogenous ADAR for Programmable Editing of RNA) are innovative RNA base-editing platforms that have recently been engineered to perform programmable base conversions on target RNAs mediated by ADAR enzymes in mammalian cells. Thus, these four currently characterized RNA-editing systems constitute novel molecular tools with compelling programmability, specificity, and efficiency that show us some creative ways to take advantage of the engineered deaminases for precise base editing. Moreover, the advanced engineering of these systems permits editing of full-length transcripts containing disease-causing point mutations without the loss of genomic information, providing an attractive alternative for research and in the therapeutic setting if the challenges encountered in off-target edits and delivery are appropriately addressed. Here, I present an analytical approach of the current status and rapid progress of the novel ADAR-mediated RNA-editing systems when highlighting the qualities of each new RNA-editing platform and how these RNA-targeting strategies could be used to recruit human ADARs on endogenous transcripts, not only for our understanding of RNA-modification-mediated regulation of gene expression but also for editing clinically relevant mutations in a programmable and straightforward manner.

中文翻译：

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用于 ADAR 介导的 RNA 编辑的新型工程可编程系统


最常见的 RNA 转录后修饰形式之一是腺苷向肌苷 (A-to-I) 的转化，这是由作用于 RNA (ADAR) 酶的腺苷脱氨酶介导的。 CRISPR/Cas 系统的出现激励研究人员积极致力于基础研究和生物医学应用的可编程 RNA 引导机器的工程设计。在这方面，CIRTS（CRISPR-Cas启发的RNA靶向系统）、RESCUE（用于特定C到U交换的RNA编辑）、RESTORE（将内源ADAR招募到特定转录本以进行寡核苷酸介导的RNA编辑）和LEAPER（利用内源ADAR）用于RNA的可编程编辑）是创新的RNA碱基编辑平台，最近被设计用于在哺乳动物细胞中由ADAR酶介导的靶RNA上执行可编程碱基转换。因此，这四种目前表征的RNA编辑系统构成了具有引人注目的可编程性、特异性和效率的新型分子工具，向我们展示了一些利用工程脱氨酶进行精确碱基编辑的创造性方法。此外，这些系统的先进工程允许编辑包含致病点突变的全长转录本，而不会丢失基因组信息，如果在脱靶编辑和传递中遇到挑战，这为研究和治疗环境提供了一个有吸引力的替代方案得到适当解决。 在这里，我介绍了新型 ADAR 介导的 RNA 编辑系统的现状和快速进展的分析方法，同时强调了每个新的 RNA 编辑平台的质量以及如何使用这些 RNA 靶向策略来招募人类 ADAR内源转录本，不仅可以帮助我们了解 RNA 修饰介导的基因表达调控，还可以以可编程且直接的方式编辑临床相关突变。