At its core, genomic editing involves the use of engineered nucleases, which create double-stranded breaks at specific locations within the genome. The most popular system, CRISPR-Cas9, makes use of a guide RNA to direct the Cas9 protein to the target site. This break can then be repaired by the cell's natural DNA repair mechanisms, either by non-homologous end joining (NHEJ) or homology-directed repair (HDR).