Dystrophin (DMD) pre-mRNA exon 45 splice site (DMD exon 45)

The Dystrophin (DMD) pre-mRNA exon 45 splice site is a specific sequence within the DMD gene transcript that serves as a therapeutic target for antisense oligonucleotides (NCBI Gene ID: 1756). In patients with Duchenne muscular dystrophy (DMD) who have deletions amenable to exon 45 skipping, the reading frame of the DMD gene is disrupted, leading to a complete lack of functional dystrophin protein (PubMed: 33631130). By targeting the splice site or exonic splicing enhancers of exon 45, drugs like casimersen induce the cellular machinery to skip this exon during mRNA processing (FDA: Amondys 45 Prescribing Information). This restoration of the reading frame allows for the production of a truncated but partially functional dystrophin protein, similar to that found in the milder Becker muscular dystrophy. This approach aims to slow the progression of muscle weakness and loss of ambulation in affected individuals. Clinical monitoring involves measuring dystrophin expression in muscle biopsies and verifying the presence of skipped mRNA transcripts.

Other names

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

Casimersen is an antisense oligonucleotide that binds to the exon 45 splice site of the dystrophin (DMD) pre-mRNA, sterically blocking the splicing machinery and inducing the skipping of exon 45 to restore the reading frame (FDA: Amondys 45 Prescribing Information).