The emergence of clustered regularly interspaced short palindromic repeat (CRISPR) nucleases has transformed biotechnology by providing an easy, efficient, and versatile platform for editing DNA. However, traditional CRISPR-based technologies initiate editing by activating DNA double-strand break (DSB) repair pathways, which can cause adverse effects in cells and restrict certain therapeutic applications of the technology. To this end, several new CRISPR-based modalities have been developed that are capable of catalyzing editing without the requirement for a DSB. Here, we review three of these technologies: base editors, prime editors, and RNA-targeting CRISPR-associated protein (Cas)13 effectors. We discuss their strengths compared to traditional gene-modifying systems, we highlight their emerging therapeutic applications, and we examine challenges facing their safe and effective clinical implementation.

成簇的规则间隔短回文重复 (CRISPR) 核酸酶的出现通过为编辑 DNA 提供了一个简单、高效和多功能的平台，改变了生物技术。然而，传统的基于 CRISPR 的技术通过激活 DNA 双链断裂 (DSB) 修复途径来启动编辑，这可能会对细胞造成不利影响并限制该技术的某些治疗应用。为此，已经开发了几种新的基于 CRISPR 的模式，它们能够在不需要 DSB 的情况下催化编辑。在这里，我们回顾了其中三种技术：碱基编辑器、主编辑器和靶向 RNA 的 CRISPR 相关蛋白 (Cas)13 效应器。我们讨论了它们与传统基因修饰系统相比的优势，我们强调了它们新兴的治疗应用，