Researchers introduced Prime‑Editing‑Based Inversion with Enhanced Performance (PIE), a technique that enables efficient, large‑scale inversion of genomic DNA in mammalian cells. PIE improves on prime editing to invert megabase‑scale segments with higher precision and lower off‑target rearrangements, enabling new models of structural variants and potential therapeutic strategies for inversion‑driven diseases. The method provides a platform for functional studies of chromosomal architecture and offers a potential route to correct pathogenic inversions; next steps include delivery optimization and assessment of long‑term genomic stability.