Official websites use. Share sensitive information only on official, secure websites. Corresponding author Jenna A. Wood, Sarepta Therapeutics, Inc. Antisense RNA technology is a strategy for the treatment of Duchenne muscular dystrophy DMD , a progressive and universally fatal X-linked neuromuscular disease caused by frameshift mutations in the gene encoding dystrophin. Phosphorodiamidate morpholino oligomers PMOs are an antisense RNA platform that is used clinically in patients with DMD to facilitate exon skipping and production of an internally truncated, yet functional, dystrophin protein.
It was evaluated in mdx mice for exon 23 skipping, dystrophin production, and functional efficacy. Single-dose RC dose dependently increased exon skipping and dystrophin protein levels in striated muscle and is associated with improvements in muscle function.
Dystrophin protein levels were durable for 60 days. Keywords: MT: oligonucleotides: therapies and applications, Duchenne muscular dystrophy, dystrophin, exon-skipping therapy, neuromuscular disease, peptide-conjugated phosphorodiamidate morpholino oligomer.
Wood and colleagues show that a phosphorodiamidate morpholino oligomer conjugated to a proprietary cell-penetrating peptide PPMO dose dependently increased exon skipping and dystrophin levels in muscles of mdx mice, resulting in functional improvement. Duchenne muscular dystrophy DMD is a rare, progressive, fatal, degenerative neuromuscular disease with X-linked recessive inheritance caused by mutations in the DMD gene, encoding dystrophin.
One current therapeutic strategy for DMD is the use of rationally designed antisense oligonucleotides ASOs that target specific sequences within the pre-mRNA transcript and modulate alternative splicing or block aberrant, disease-causing splice sites.
