The currently available RESCUE RNA base editing system demonstrates considerable potential for the treatment of genetic diseases at the transcriptional level. However, the relatively high incidence of off-target events hampers the precise RNA editing, thereby limiting its use in the clinical setting. This study describes a new RNA base editing method, named ecRESCUE, which utilizes inducible stabilization of the protein ecDHFR DD fused at the C-terminal of the original RESCUE system. In vitro experiments in 293T cells showed that the ecRESCUE editor markedly reduced the incidence of off-target single nucleotide polymorphisms without affecting the RNA A-to-I and C-to-U base editing efficiency. Altogether, these results demonstrate that the inducible ecRESCUE system represents an attractive approach to regulate and improve the outcome of the available RNA base editor with reduced off-targeting activity.

中文翻译：

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ecRESCUE：一种新型 ecDHFR 调节的 RESCUE 系统，其 RNA 脱靶活性降低

目前可用的 RESCUE RNA 碱基编辑系统在转录水平上显示出治疗遗传疾病的巨大潜力。然而，脱靶事件的相对高发生率阻碍了精确的 RNA 编辑，从而限制了其在临床环境中的使用。本研究描述了一种名为 ecRESCUE 的新 RNA 碱基编辑方法，该方法利用融合在原始 RESCUE 系统 C 端的蛋白质 ecDHFR DD 的诱导稳定性。在 293T 细胞中进行的体外实验表明，ecRESCUE 编辑器显着降低了脱靶单核苷酸多态性的发生率，而不影响 RNA A-to-I 和 C-to-U 碱基编辑效率。共，