Dystrophin (DMD) pre-messenger RNA exon 2 splice acceptor and donor regions (DMD exon 2 splice sites)

The Dystrophin (DMD) pre-messenger RNA exon 2 splice acceptor and donor regions are specific nucleotide sequences at the boundaries of the second exon that guide the spliceosome during mRNA processing. These regions are a primary therapeutic target for patients with Duchenne muscular dystrophy (DMD) who possess an exon 2 duplication, which is the most common duplication mutation in the DMD gene (Flanigan et al., 2011, Human Mutation). Therapeutic strategies, such as the AAV-U7-ACCA (AT702) gene therapy, utilize antisense sequences to bind these regions and sterically hinder the splicing machinery (Waldrop et al., 2022, JAMA Neurology). This intervention induces the skipping of the duplicated exon, thereby restoring the correct reading frame and allowing for the production of functional dystrophin protein. Clinical evidence from early-phase trials (NCT04240314) indicates that targeting these splice sites can lead to significant dystrophin restoration in muscle fibers. This precision medicine approach is designed to address the underlying genetic defect in a specific subset of DMD patients, potentially slowing or halting disease progression.

Other names

DMD exon 2 splice junctionsDystrophin exon 2 acceptor and donor sitesDMD pre-mRNA exon 2 SSDystrophin exon 2 splice sites

Antisense-mediated exon skipping by blocking spliceosome assembly at the exon 2 acceptor and donor sites