antisense oligonucleotide targeting MYPN exon 14

Antisense oligonucleotide targeting MYPN exon 14 is an investigational RNA-targeted therapy designed for the treatment of congenital myopathy caused by pathogenic variants in the MYPN gene. Specifically, it targets a homozygous nonsense variant in exon 14 (c.2986C>T, p.Arg996Ter) that creates a novel donor splice site, leading to aberrant pre-mRNA splicing, a frameshift, and premature termination. By binding to the pre-mRNA, the antisense oligonucleotide (ASO) induces skipping of the entire exon 14, restoring MYPN mRNA levels and potentially rescuing the expression of myopalladin, the protein encoded by MYPN. This therapeutic approach has been evaluated in preclinical minigene systems and patient-derived dermal fibroblasts.