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

The dystrophin pre-mRNA exon 44 splice recognition region is a specific sequence within the DMD gene transcript that regulates the inclusion of exon 44 during mRNA processing (NCBI, NBK1119). In Duchenne muscular dystrophy (DMD) patients with specific deletions, such as those of exon 45 or exons 43-45, the reading frame is disrupted, leading to a lack of functional dystrophin protein (PubMed, 31431440). This region serves as a therapeutic target for antisense oligonucleotides (ASOs) that induce exon skipping. By binding to the splice recognition sequences, these drugs mask exon 44 from the spliceosome, causing it to be excluded from the mature mRNA. This process restores the translational reading frame, allowing for the production of a truncated but partially functional dystrophin protein (Sarepta Therapeutics, 2024). Clinical candidates like NS-089/NCNP-02 and SRP-5044 are designed to target this region to treat patients amenable to exon 44 skipping (Nippon Shinyaku, 2023). Successful modulation of this target is typically monitored through the expression of de novo dystrophin in muscle biopsies and improvements in motor function. Safety considerations for drugs targeting this region include potential renal toxicity and injection site reactions common to the ASO class.

Other names

DMD pre-mRNA exon 44Dystrophin exon 44Exon 44 of the DMD geneDystrophin pre-mRNA exon 44 splice site

Antisense oligonucleotide-mediated exon skipping to restore the mRNA reading frame.