We exploit both ESE mechanisms and exon symmetry to maximizethe probability of gene ablation. In our previous work we have shown that CRISPR/Cas9-induced alterations in ESEs are highly related to exon skipping events.
Now, we define exon symmetry as the match between the starting and ending phase of an exon. If the phases are the same, the exon is symmetric; if the phases are different, the exon is asymmetric. Inducing a skip of an Asymmetric exon will cause the effect of a frame-shift deletion. This can, in turn, generate a Premature Termination Codon (PTC) that induces gene-knockout via nonsense-mediated decay (NMD). Skipping a symmetric exon, on the other hand, will preserve the reading frame and may rescue a shorter version of the protein in question.