迭代重组酶技术在千碱基到百万碱基尺度上高效和精确的基因组工程，这一成果由中国科学院遗传与发育生物学研究所高彩霞小组经过不懈努力而取得。2025年8月4日出版的《细胞》发表了这项成果。

小组提出了可编程染色体工程（PCE）和RePCE，两种可编程染色体编辑系统，可以在植物和人类细胞中进行无疤痕的千碱基到百万碱基的DNA操作。通过高通量工程，研究团队获得了可逆性降低10倍的Lox位点，并应用AI辅助重组酶工程方法（AiCErec）生成了重组效率为野生型3.5倍的Cre变体。结合Re-pegRNA介导的无疤痕策略进一步提高了编辑精度，在染色体水平上允许无疤痕插入、缺失、替换、倒位和易位。主要应用包括315 kb的水稻抗除草剂反转，无疤痕染色体，以及12 Mb的人类疾病相关位点反转。这些进展显著拓宽了基因组编辑在分子育种、治疗开发和合成生物学方面的应用范围。

据介绍，基因组编辑技术在实现高等生物的精确、大规模DNA操作方面面临挑战，包括低效率、有限的编辑规模和类型，以及保留不需要的序列，如重组位点（“疤痕”）。

附：英文原文

Title: Iterative recombinase technologies for efficient and precise genome engineering across kilobase to megabase scales

Author: Chao Sun, Hongchao Li, Yijing Liu, Yunjia Li, Rui Gao, Xiaoli Shi, Hongyuan Fei, Jinxing Liu, Ronghong Liang, Caixia Gao

Issue&Volume: 2025-08-04

Abstract: Genome editing technologies face challenges in achieving precise, large-scale DNA manipulations in higher organisms, including inefficiency, limited editing scales and types, and the retention of undesired sequences such as recombination sites (“scars”). Here, we present programmable chromosome engineering (PCE) and RePCE, two programmable chromosome editing systems enabling scarless kilobase-to-megabase DNA manipulations in plants and human cells. Through high-throughput engineering, we obtained Lox sites with a 10-fold reduced reversibility and applied an AI-assisted recombinase engineering method (AiCErec) to generate Cre variants with 3.5 times the recombination efficiency of the wild type. Incorporation of a Re-pegRNA-mediated scar-free strategy further enhanced editing precision, allowing scarless insertions, deletions, replacements, inversions, and translocations at the chromosomal level. Key applications include a 315-kb inversion in rice conferring herbicide resistance, scarless chromosome fusions, and a 12-Mb inversion at human disease-related sites. These advances significantly broaden the scope of genome editing applications in molecular breeding, therapeutic development, and synthetic biology.

DOI: 10.1016/j.cell.2025.07.011

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00800-1