Nature：最精准的先导编辑器来了

Core Viewpoint - The article discusses the advancements in prime editing technology, particularly the development of the next-generation prime editor (vPE) that significantly reduces genomic errors compared to its predecessor, the original prime editor (PE) [3][4][5]. Group 1: Prime Editing Technology - Prime Editor (PE) is an advanced CRISPR gene editing tool developed by Professor Liu Ruqian's team in 2019, capable of editing and repairing 89% of 75,000 known pathogenic human genetic mutations [3][5]. - The editing process involves the prime editor binding to the genomic target, creating a single-strand DNA cut, and using pegRNA to guide the insertion or replacement of new DNA sequences [5][6]. - A significant challenge remains in eliminating errors produced as byproducts of prime editing, specifically insertion/deletion mutations (indels) that can lead to unpredictable and potentially harmful DNA sequences [5][6]. Group 2: Advances in Error Reduction - The research team identified key factors driving indel error formation, including the potential for the edited 3' new strand to extend beyond the pegRNA template and the conversion of single-strand cuts into double-strand breaks due to mismatch repair [6][7]. - By engineering the prime editor to induce instability in the competitive 5' strand, the team discovered a significant reduction in indel errors, leading to the development of the next-generation prime editor (vPE) [7][9]. - The vPE demonstrates a substantial improvement in editing efficiency while reducing the indel error rate to 1/60 of the original prime editor, with errors occurring only once every 543 edits [9].