Researchers led by Professor Gao Caixia from the Chinese Academy of Sciences have developed novel Programmable Chromosome Engineering (PCE) systems enabling megabase-scale precision genome editing in eukaryotic cells. By addressing key limitations of the Cre-Lox system, including reversible recombination and residual genomic scars, the team engineered asymmetric Lox sites and an optimized Cre recombinase variant using AI-derived constraints. This led to highly efficient, scarless recombination strategies facilitating large-scale chromosomal manipulations, particularly in plants. Their approach opens new frontiers in genome engineering with implications for crop improvement and biotechnology.