Antisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.

ABSTRACT: Dysferlinopathies are debilitating autosomal recessive muscular dystrophies caused by mutations in the DYSF gene, encoding dysferlin, a protein crucial for sarcolemmal homeostasis and membrane resealing. Currently, no therapies exist for dysferlinopathies. Dysferlin features a modular structure with multiple calcium-dependent C2 lipid-binding domains. Clinical reports of mild, late-onset phenotypes suggest partial retention of functionality despite missing C2 domains, supporting exon-skipping therapies using antisense oligonucleotides (ASOs). In this study, we identified a patient-derived muscle cell line with a splice site mutation in DYSF intron 26, causing exon 26 exclusion, an out-of-frame transcript, and no detectable dysferlin protein. We hypothesized that skipping D

SUBMITTER: Anwar S 

PROVIDER: S-EPMC11834094 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature