Oligonucleotide-based therapies have potential for treating a range of inherited neuromuscular disorders via modulating gene expression e.g. via splice modulation or RNA silencing. The classical example is Duchenne muscular dystrophy (DMD), where modulation of pre-mRNA splicing of the DMD gene can restore a viable reading frame and the expression of functional protein. This approach is currently being evaluated in clinical trials. However, a major challenge in the application of such approaches to neuromuscular disease is poor delivery to affected tissues including skeletal muscle, heart and to the nervous system across the blood brain barrier. We have developed a range of peptide- and extracellular vesicle-based platform technologies to overcome this challenge. Peptide-oligonucleotide compounds provide greatly improved delivery and enhanced potency and are being developed for future clinical applications in both DMD and for other neuromuscular disorders, such as spinal muscular atrophy. Future prospects will be discussed.
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