Dystrophin pre-mRNA exon 45 splice-regulatory sequence (DMD exon 45)

The dystrophin pre-mRNA exon 45 splice-regulatory sequence is a specific region within the DMD gene transcript that governs the inclusion of exon 45 during the splicing process (Sarepta Therapeutics, 2021). In patients with Duchenne muscular dystrophy (DMD) who have specific deletions, such as those missing exon 44, the reading frame of the mRNA is disrupted, leading to a complete lack of functional dystrophin protein (FDA, 2021). By targeting this regulatory sequence with antisense oligonucleotides like casimersen or viltolarsen, the splicing machinery is redirected to skip exon 45 (Wagner et al., 2021; FDA, 2020). This "exon skipping" strategy restores the open reading frame, allowing for the production of a truncated but partially functional dystrophin protein, similar to that found in the milder Becker muscular dystrophy (PubMed, 2021). This therapeutic approach aims to slow disease progression and improve muscle function in affected individuals (NIH, 2021). Monitoring for renal toxicity is essential when targeting this sequence with phosphorodiamidate morpholino oligomers (FDA, 2021).

Other names

DMD exon 45Dystrophin exon 45Exon 45 of the DMD geneDystrophin pre-mRNA exon 45

Antisense oligonucleotide binding to the target sequence to sterically block the splicing machinery, resulting in the exclusion (skipping) of exon 45 from the mature mRNA transcript (FDA, 2021; FDA, 2020).