Dystrophin (DMD) pre-mRNA exon 44 splice-regulatory region (DMD exon 44)

The DMD pre-mRNA exon 44 splice-regulatory/junction region is a specific sequence within the dystrophin gene transcript that regulates the inclusion of exon 44 during mRNA processing (Aartsma-Rus et al., 2009). In patients with Duchenne muscular dystrophy (DMD) who have specific mutations, such as deletions of exon 45, the reading frame is disrupted, preventing the production of functional dystrophin (Heemskerk et al., 2011). This region serves as a therapeutic target for antisense oligonucleotides (ASOs) designed to induce exon skipping. By binding to this splice-regulatory region, ASOs like Atececa (NS-089/NCNP-02) and SRP-4044 sterically block the splicing machinery, causing exon 44 to be bypassed (Nippon Shinyaku, 2023; Sarepta Therapeutics, 2024). This restoration of the reading frame allows for the synthesis of a truncated but partially functional dystrophin protein, which aims to slow the progression of muscle wasting. Clinical monitoring of this target involves measuring dystrophin protein expression in muscle tissue and evaluating improvements in physical mobility (Nippon Shinyaku, 2023).

Other names

DMD exon 44 splice junctionDystrophin exon 44DMD pre-mRNA exon 44

Antisense oligonucleotides bind to the splice-regulatory sequences or splice junctions of exon 44, sterically hindering the spliceosome and causing the exon to be excluded from the mature mRNA transcript to restore the reading frame (Aartsma-Rus et al., 2009).