The paper cited below describes work in a dog model of Duchenne muscular dystrophy (DMD). One in 3500 male human births have DMD, a devastating congenital disease caused by a non-functioning protein in muscle called dystrophin. Short sections of a synthetic material that resembles nucleic acid can be used to bind intron-exon boundaries in pre-mRNA, redirecting splicing. Many mutations causing DMD are frameshifting mutations, insertions or deletions that shift the boundaries of codons during translation. Redirecting splicing can correct the frameshift by removing an exon to cause a new frameshift so that the mutation and the exon skip cancel each other out and return the sequence downstream to in-frame translation.
Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs Annals of Neurology 2009 [epub ahead of print] doi 10.1002/ana.21627
Videos of treated and control dystrophic dogs:
Video 1, Non-treated Dystrophic Dog, 7 months old
Video 2, Non-treated Dystrophic Dog, 7 months old
Video 3, Treated Dystrophic Dog, 7 months old, after 5 x Weekly 120 mg/Kg Morpholino oligo cocktail injections.
Video 4, Treated Dystrophic Dog, 4 months old, after 7 × 200 mg/Kg Morpholino oligo cocktail injections.
Video 5, Treated Dystrophic Dog, 7 months old, ater 11 × 120 mg/Kg Morpholino oligo cocktail injections.
NIH press release on Morpholinos for Duchenne muscular dystrophy in a dog model of DMD:
Children’s National Medical Center press release: