Genome editing methods have commonly relied on the initial introduction of double-stranded DNA breaks (DSBs), resulting in stochastic insertions, deletions, and translocations at the target genomic locus. To achieve gene correction, these methods typically require the introduction of exogenous DNA repair templates and low-efficiency homologous recombination processes. In this review, we describe alternative, mechanistically motivated strategies to perform chemistry on the genome of unmodified cells without introducing DSBs. One such strategy, base editing, uses chemical and biological insights to directly and permanently convert one target base pair to another. Despite its recent introduction, base editing has already enabled a number of new capabilities and applications in the genome editing community. We summarize these advances here and discuss the new possibilities that this method has unveiled, concluding with a brief analysis of future prospects for genome and transcriptome editing without double-stranded DNA cleavage.

中文翻译：

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编辑没有双链DNA断裂的基因组

基因组编辑方法通常依赖于最初引入双链DNA断裂（DSB），导致目标基因组基因座处的随机插入，缺失和易位。为了实现基因校正，这些方法通常需要引入外源DNA修复模板和低效率的同源重组过程。在这篇综述中，我们描述了在不引入DSB的情况下对未修饰细胞的基因组进行化学反应的，具有机械动力的替代策略。一种这样的策略，即碱基编辑，利用化学和生物学洞察力将一个目标碱基对直接永久地转换为另一对碱基。尽管最近进行了介绍，但碱基编辑已经在基因组编辑社区中启用了许多新功能和应用程序。