Researchers described a two‑step genome‑editing strategy that enables construction of full‑length humanized mouse models, overcoming limitations tied to divergent regulatory landscapes between species. The approach stitches large human genomic segments into the mouse genome in a staged process, preserving human regulatory elements and gene architecture to better recapitulate human gene function in vivo. The method promises more faithful preclinical platforms for studying human gene regulation, drug responses, and disease modeling. Developers of genetic medicines and regulators will be interested in how these models predict human biology compared with conventional knock‑ins, and whether they accelerate translational validation of candidate therapies.