Figure 3.

Gene correction of the HbS mutation with donor templates via homology direct repair (HDR).

Gene correction of the HbS mutation requires a Cas9:gRNA complex to create a DSB (scissors) and a donor template to specify the desired change (ssODN or rAAV6 donors shown). The resultant outcomes show the correct HDR integration with the wild type GAG (green text) substituted for the pathogenic GTG (red text). Additionally, repair via the error-prone and dominant DNA repair pathway in mammalian cells will result in indels and knockout (KO) of the HBB gene. DSB: double-strand break; ssODN: single-stranded oligodeoxynucleotides.