Recombinant adeno-associated virus (rAAV) based genome engineering is a genome-editing platform centered on the use of rAAV vectors that enables insertion, deletion or substitiution of DNA sequences into the genomes of live mammalian cells. The technique builds on Capecchi and Smithies’ Nobel Prize–winning discovery that homologous recombination (HR), a natural hi-fidelity DNA repair mechanism, can be harnessed to perform precise genome alterations in mice.