Journal of Genetic Medicine : eISSN 2383-8442 / pISSN 1226-1769

Fig. 1.

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Fig. 1. Mechanism of antisense oligonucleotides (ASO). (A) RNA cleavage with gapmer ASOs. Gapmer ASOs bind to target RNA, forming a duplex that activates RNase H, which degrades the RNA. This reduces the production of toxic proteins while allowing some residual protein function. (B) Splice modulation. ASOs target and block abnormal splice sites caused by mutations, redirecting splicing to produce functional proteins, as observed in certain genetic disorders like spinal muscular atrophy. (C) Exon skipping. ASOs bind to specific exons, preventing their inclusion during splicing. This generates a shorter protein that retains partial functionality, an approach used in conditions like Duchenne muscular dystrophy. (D) Upregulation of wild-type allele. ASOs can block poison exons to bypass nonsense-mediated decay and restore functional protein production, as seen in SCN1A for Dravet syndrome. They can also target antisense transcripts to boost gene expression, such as Ube3a in Angelman syndrome, or inhibit uORFs to enhance translation of functional proteins.
Journal of Genetic Medicine 2024;21:41-50 https://doi.org/10.5734/JGM.2024.21.2.41
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