In addition to combating cancers, inhibiting DNA-PK, including DNA-PKcs, can facilitate HDR-mediated knock-in by reducing the NHEJ events after DSBs induced by nucleases, such as I-Sce1 meganuclease, Zinc finger nucleases, TALENs, or CRISPR-Cas systems [13,14,15,16,17]. The gene discussed is PRKDC; the disease is cancer.