Gene-editing tools are evolving rapidly, from the first CRISPR–Cas systems to base editing and, more recently, prime editing. Unlike CRISPR–Cas systems, base editing does not require double-strand breaks; neither does prime editing, and it supports greater editing power — including targeted insertions and deletions. In April, the US Food and Drug Administration cleared the investigational new drug application for PM359 (from Prime Medicine), making it the first prime editor to enter the clinic. Designed as a one-time treatment to correct a mutation that causes chronic granulomatous disease, PM359 will first be evaluated in adult patients in a phase 1/2 study (NCT06559176) — with the aim of then testing it in adolescents and children, if it is deemed safe. Another technique, epigenome editing, enables gene silencing without any alteration to the gene itself. Instead, the editing machinery targets the heritable (but reversible) structures around genes that determine their expression. Although still in the preclinical phase, it adds to the array of new gene-editing tools that promise greater flexibility and safety.

Original references: prime medicine https://go.nature.com/4esxKzk (29 April 2024); Nature 627, 416–423 (2024)

基因编辑工具正在迅速发展，从最初的 CRISPR-Cas 系统到碱基编辑，再到最近的 prime 编辑。与 CRISPR-Cas 系统不同，碱基编辑不需要双链断裂;Prime Editing 也不支持，它支持更强大的编辑功能 — 包括有针对性的插入和删除。4 月，美国食品药品监督管理局批准了 PM359 的研究性新药申请（来自 Prime Medicine），使其成为第一个进入临床的 prime 编辑。PM359 被设计为一次性治疗，用于纠正导致慢性肉芽肿病的突变，将首先在 1/2 期研究 （NCT06559176） 中对成年患者进行评估——目的是在认为安全的情况下在青少年和儿童中进行测试。另一种技术是表观基因组编辑，可以在不改变基因本身的情况下进行基因沉默。相反，编辑机制针对决定其表达的基因周围的可遗传（但可逆）结构。尽管仍处于临床前阶段，但它增加了一系列新的基因编辑工具，有望获得更大的灵活性和安全性。

原始参考资料：Prime Medicine https://go.nature.com/4esxKzk（2024 年 4 月 29 日）;自然627， 416–423 （2024）