Starting in the late 1990s, scientists realized they could take advantage of this naturally occurring cellular splicing to downplay genetic mutations into less harmful ones.
An antisense oligonucleotide is a synthesized short nucleic acid polymer, typically fifty or fewer base pairs in length that will bind to the mutation site in the pre-messenger RNA, to induce exon skipping.
[3] The AON binds to the mutated exon, so that when the gene is then translated from the mature mRNA, it is “skipped” over, thus restoring the disrupted reading frame.
Successful treatment by way of exon skipping could lead to a mostly functional dystrophin protein, and create a phenotype similar to the less severe Becker muscular dystrophy (BMD).
Mutations that disrupt the open reading frame within dystrophin create prematurely truncated proteins that are unable to perform their job.
[6] Comparatively, mutations that do not upset the open reading frame, lead to a dystrophin protein that is internally deleted and shorter than normal, but still partially functional.
[7] A third antisense oligonucleotide, viltolarsen (Viltepso), targeting dystrophin exon 53 was approved for medical use in the United States in August 2020.