ABSTRACT

RNA editing by cytosine and adenosine deaminases changes the identity of the edited bases. While cytosines are converted to uracils, adenines are converted to inosines. If coding regions of mRNAs are affected, the coding potential of the RNA can be changed, depending on the codon affected. The recoding potential of nucleotide deaminases has recently gained attention for their ability to correct genetic mutations by either reverting the mutation itself or by manipulating processing steps such as RNA splicing. In contrast to CRISPR-based DNA-editing approaches, RNA editing events are transient in nature, therefore reducing the risk of long-lasting inadvertent side-effects. Moreover, some RNA-based therapeutics are already FDA approved and their use in targeting multiple cells or organs to restore genetic function has already been shown. In this review, we provide an overview on the current status and technical differences of site-directed RNA-editing approaches. We also discuss advantages and challenges of individual approaches.

 抽象的

胞嘧啶和腺苷脱氨酶进行的 RNA 编辑改变了编辑碱基的特性。当胞嘧啶转化为尿嘧啶时，腺嘌呤转化为肌苷。如果 mRNA 的编码区受到影响，RNA 的编码潜力可能会发生变化，具体取决于受影响的密码子。核苷酸脱氨酶的重新编码潜力最近因其通过恢复突变本身或通过操纵RNA剪接等加工步骤来纠正基因突变的能力而受到关注。与基于 CRISPR 的 DNA 编辑方法相比，RNA 编辑事件本质上是短暂的，因此降低了长期意外副作用的风险。此外，一些基于 RNA 的疗法已经获得 FDA 批准，并且已经证明它们可用于靶向多个细胞或器官以恢复遗传功能。在这篇综述中，我们概述了定点 RNA 编辑方法的现状和技术差异。我们还讨论了各种方法的优点和挑战。