Engineered prime editors with minimal genomic errors

doi:10.1038/s41586-025-09537-3

2025-09-17

Vikash P. Chauhan *

Phillip A. Sharp *

Róbert Langer *

DOI：10.1038/s41586-025-09537-3

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摘要

En 中文

碱基编辑器通过将新序列写入缺口DNA 3′末端的延伸部分来实现程序化的基因组修饰1。这些被编辑的3′新链必须取代竞争性的5′链才能安装编辑，然而偏向于保留竞争性的5′链会降低效率，并可能导致indel错误2。在此，我们发现缺口末端降解，与竞争性5′链失稳一致，可被能够放松缺口定位的Cas9-nickase突变所促进。我们利用这一机制工程化设计出高效的碱基编辑器，其indel错误率显著降低。将这种错误抑制策略与最新的效率提升架构相结合，我们设计了一种下一代碱基编辑器（vPE）。与之前的编辑器相比，vPE具有相当的效率，但indel错误率低至原来的1/60，使编辑:indel比值高达543:1。开发出工程化的碱基编辑器系统，以减少基因组编辑过程中不必要插入或删除的发生。

Keyword:

Prime editing

Genome editing

Indel errors

Cas9-nickase

Next-generation prime editor

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期刊

Nature

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48.5

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1.8W

被引数:

96.5W

机构

Massachusetts Institute of Technology

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2.4K

论文数: 1.1K

被引数: 8

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