Dystrophin pre-messenger RNA exon 23 (DMD exon 23)

Dystrophin pre-messenger RNA (pre-mRNA) exon 23 is a specific segment of the DMD gene transcript that serves as a primary target for splice-switching therapies in Duchenne muscular dystrophy (DMD) (Mann et al., 2001, PNAS). In the mdx mouse model, the most common animal model for DMD, a nonsense mutation in exon 23 prevents the production of functional dystrophin protein, leading to progressive muscle degeneration (Lu et al., 2003, Nature Medicine). Therapeutic strategies targeting this exon utilize antisense oligonucleotides (ASOs) to mask splice sites or exonic splicing enhancers, causing the cellular splicing machinery to skip exon 23 (Aartsma-Rus et al., 2004, Gene Therapy). This process restores the mRNA reading frame, allowing for the translation of a truncated but internally functional dystrophin protein. Although mutations in exon 23 are relatively rare in human DMD patients compared to other hotspots like exon 51, the successful restoration of dystrophin via exon 23 skipping in preclinical models established the foundation for the development of FDA-approved exon-skipping drugs (Heemskerk et al., 2009, Molecular Therapy).

Other names

DMD pre-mRNA exon 23Dystrophin exon 23mdx mutation siteDMD exon 23

Antisense oligonucleotide-mediated steric hindrance of splicing signals to induce exon skipping and restore the reading frame of the dystrophin transcript.