Researchers reported a two-step genome editing strategy that creates full-length humanized mouse models, overcoming limitations in regulatory sequence divergence between species. The method inserts contiguous human genomic regions while preserving chromatin context, enabling more faithful recapitulation of human gene regulation in vivo. The advance improves the fidelity of preclinical functional studies for human-specific regulatory elements and noncoding variants, offering a scalable route to generate mouse models that better predict human responses to therapeutics and genetic perturbations.