Figure 2.

Multiple genetic modifications and their therapeutic applications. Upon a double-strand break (DSB), DNA can be repaired by two mechanisms, non-homologous end joining (NHEJ) or homology directed repair (HDR). The first mechanism frequently results in insertions or deletions (indels). Inducing indels can be used for disruption of coding sequences or to restore the reading frame, for frameshift mutations. For HDR to occur, a DNA template containing the desired modification, with homology arms flanking the target site is required. This approach is recommended when specific DNA modifications are intended, as this is an error-free repair mechanism. HDR can result in the following modifications, depending on the template used—single nucleotide variant (SNV), insertion of coding sequences under their own endogenous promoter control or alternative endogenous promoters, addition of genes (promoter + cDNA) in safe harbor loci, and replacement of partial coding sequences (one or multiple exons).