Core Viewpoint - The research team from the Chinese Academy of Sciences has developed a novel programmable chromosome-level large segment DNA manipulation technology, PCE, which enables precise editing of DNA at the kilobase to megabase level in eukaryotic genomes, representing a significant breakthrough in the field of genetic engineering [1][2]. Group 1: Technology Development - The new method addresses the core challenge of precise manipulation of large segments of DNA, which existing tools struggle with in terms of efficiency, scale, precision, and diversity [2]. - The research team has created two programmable chromosome editing systems, PCE and RePCE, which allow for precise and seamless manipulation of ultra-large segments of DNA [2][3]. - Three key technological innovations have been achieved to enhance the capabilities of large segment DNA editing, including the development of a high-throughput recombination site modification platform, optimization of Cre recombinase using artificial intelligence, and the creation of a "no trace editing strategy" called Re-pegRNA [3]. Group 2: Applications and Implications - The new technology has the potential to revolutionize crop trait improvement and genetic disease treatment by enabling the manipulation of genomic structural variations [4][6]. - In traditional breeding, desirable traits are often linked with undesirable genes, but the breakthrough in large segment DNA editing could lead to new breeding strategies that eliminate these undesirable traits while enhancing beneficial ones [4]. - The technology has already been successfully applied to create a rice variety with a precise inversion of 315 kilobases that is resistant to herbicides [5]. - In the field of genetic disease treatment, this technology may provide new therapeutic approaches for diseases caused by chromosomal abnormalities and accelerate the construction of artificial chromosomes, which is crucial for synthetic biology and other emerging fields [6].

Core Insights - The article discusses a revolutionary breakthrough in genome editing technology, specifically the development of a new programmable chromosome-level DNA manipulation technique called PCE, which enables precise editing of DNA segments ranging from thousands to millions of base pairs [1][2]. Group 1: Technology Development - The research team has developed two programmable chromosome editing systems, PCE and RePCE, which allow for precise manipulation of ultra-large DNA segments, effectively addressing the "scale dilemma" in genome editing [2]. - The team has achieved three key technological innovations to enhance the capabilities of ultra-large DNA precise editing [2][3]. Group 2: Technical Innovations - The first innovation involves changing the "double-gate" system to a "single-channel" system to overcome the reversibility issue of recombination reactions caused by the inherent symmetry of Lox sites, creating a new type of Lox variant that facilitates targeted editing [2]. - The second innovation utilizes artificial intelligence to optimize the Cre recombinase, resulting in a 3.5-fold increase in recombination efficiency, thereby enhancing the overall effectiveness of the editing process [3]. - The third innovation is the development of the Re-pegRNA strategy, which acts like a smart eraser to precisely identify and eliminate residual sites that could interfere with the accuracy of genome editing [3]. Group 3: Applications and Implications - The new ultra-large DNA precise editing method is expected to open new pathways for crop trait improvement and genetic disease treatment by manipulating genomic structural variations [4]. - In traditional breeding, desirable traits are often linked with undesirable genes, but the breakthrough in large segment DNA editing could lead to new breeding strategies that control fertility and eliminate linked burdens, maximizing the breeding potential of wild germplasm resources [4]. - The research team has successfully created a rice variety with a precise inversion of 315 kilobases that is resistant to herbicides, showcasing the practical application of this technology [4].