On Aug. 5, 2025, a team of Chinese researchers led by Prof. GAO Caixia from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences has developed two new genome editing technologies, known collectively as Programmable Chromosome Engineering (PCE) systems.

The study, published online in Cell, achieves multiple types of precise DNA manipulations ranging from kilobase to megabase scale in higher organisms, especially plants.

Extensive research has demonstrated the immense potential of the site-specific recombinase Cre-Lox system for precise chromosomal manipulation. However, its broader application has been hindered by three critical limitations: (1) reversible recombination reactions—stemming from the inherent symmetry of Lox sites—can negate desired edits; (2) the tetrameric nature of Cre recombinase complicates engineering efforts, hindering activity optimization; and (3) residual Lox sites after recombination may compromise editing precision.

The research team addressed each of these challenges and developed novel methods to advance the state of this technology. First, they built a high-throughput platform for rapid recombination site modification and proposed an asymmetric Lox site design. This led to the development of novel Lox variants that reduce reversible recombination activity by over 10-fold (approaching the background level of negative controls) while retaining high-efficiency forward recombination.

As a proof of concept, the researchers used this technology to create herbicide-resistant rice germplasm with a 315-kb precise inversion, showcasing its transformative potential for genetic engineering and crop improvement. This pioneering work not only overcomes the historical limitations of the Cre-Lox system but also opens new avenues for precise genome engineering in a variety of organisms.