Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology.
For the majority of Duchenne muscular dystrophy (DMD) mutations, antisense oligonucleotide (AON)-mediated exon skipping has the potential to restore a functional protein. Here we show that weekly intravenous injections of morpholino phosphorodiamidate (morpholino) AONs induce expression of functional levels of dystrophin in body-wide skeletal muscles of the dystrophic mdx mouse, with resulting improvement in muscle function. Although the level of dystrophin expression achieved varies considerably between muscles, antisense therapy may provide a realistic hope for the treatment of a majority of individuals with DMD.
Alter
Julia
J
Muscle Cell Biology, MRC Clinical Science Centre, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Lou
Fang
F
Rabinowitz
Adam
A
Yin
HaiFang
H
Rosenfeld
Jeffrey
J
Wilton
Steve D
SD
Partridge
Terence A
TA
Lu
Qi Long
QL
D000818:Animals; D001483:Base Sequence; D004334:Drug Administration Schedule; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics
D016189:Dystrophin; D020319:Oligodeoxyribonucleotides, Antisense