This strategy can be used to: (i) restore the mRNA reading frame by exon skipping in diseases such as DMD in which frame-shift deletions or non-sense mutations cause the functional protein loss; (ii) promote the inclusion of exons, as occurs in SMA where ASOs induce the inclusion of the exon 7 in the SMN2 gene; (iii) introduce an out-of-frame deletion for reducing protein expression, as in Alzheimer disease or in Amyotrophic Lateral Sclerosis (Figure 2) [67]. Here, SMN2 is linked to proximal spinal muscular atrophy.