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Prime editing is a rapidly emerging gene-editing technology that mediates targeted insertions, deletions, and base-to-base conversions, without double strand breaks or donor DNA. After first identifying the optimal prime-editing guide RNAs and the most efficient prime editors, Jang et al. apply prime editing to precisely correct the disease-causing mutations in mouse models of hereditary tyrosinemia type 1 (HT-1 mice) and Leber congenital amaurosis (LCA mice), using hydrodynamic or subretinal delivery, respectively. The treatment prevented weight loss and extended survival in HT-1 mice, and improved visual function in LCA mice, without any detectable off-target edits.