Core Viewpoint - The article discusses the revolutionary advancements in genome editing technology, particularly focusing on the development of a new programmable chromosome engineering (PCE) system that enables precise manipulation of large DNA segments ranging from kilobases to megabases, which addresses significant challenges in the field of genetic engineering [4][11]. Group 1: Technology Overview - Genome editing technology, exemplified by CRISPR and its derivatives, has made significant strides in precise editing of specific bases and short DNA fragments, but large-scale DNA editing remains a core challenge [3]. - The PCE system developed by the research team allows for efficient and precise manipulation of DNA at the chromosome level, significantly enhancing the capability to edit eukaryotic genomes [4][11]. Group 2: Technical Innovations - The research team addressed three key limitations of the Cre-Lox system, including the inherent symmetry of Lox sites, the difficulty in engineering Cre enzyme activity, and the precision of editing due to residual Lox sites after recombination [6][8]. - Innovations include a high-throughput recombination site modification platform, the development of new Lox variants with reduced recombination activity, and an engineered Cre protein variant that improves recombination efficiency by 3.5 times [6][7]. Group 3: Applications and Implications - The PCE system has successfully achieved various large-scale DNA manipulations, including the integration of an 18.8 kb DNA segment, directional replacement of a 5 kb sequence, and chromosomal inversions and deletions up to 12 Mb [7]. - This technology not only facilitates multi-gene stacking but also opens new pathways for crop trait improvement and genetic disease treatment, potentially transforming breeding strategies and synthetic biology applications [11].