Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-point^TM that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule. Pin-point is capable of efficiently modifying base pairs in the human genome with precision and low on-target indel formation. This system can potentially be applied for correcting pathogenic mutations, installing premature stop codons in pathological genes, and introducing other types of genetic changes for basic research and therapeutic development.

中文翻译：

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模块化 CRISPR 和 RNA 适体介导的碱基编辑系统的开发和表征


用于精确基因组编辑的传统 CRISPR 方法依赖于引入 DNA 双链断裂 (DSB) 和激活同源定向修复 (HDR)，这在体细胞中具有固有的遗传毒性且效率低下。无需生成 DSB 或 HDR 即可编辑目标碱基的碱基编辑 (BE) 系统的开发提供了一种替代方案。在这里，我们描述了一种名为 Pin-point ^TM的新型 BE 系统，该系统通过 gRNA 分子内的 RNA 适体招募 DNA 碱基修饰酶。 Pin-point 能够高效、精确地修改人类基因组中的碱基对，且目标插入/缺失形成率较低。该系统可潜在地应用于纠正致病突变、在病理基因中安装过早终止密码子以及引入其他类型的遗传变化以用于基础研究和治疗开发。