Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology

Nat Med. 2006 Feb;12(2):175-7. doi: 10.1038/nm1345. Epub 2006 Jan 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Drug Administration Schedule
  • Dystrophin / genetics*
  • Dystrophin / metabolism
  • Gene Expression Regulation
  • Genetic Therapy
  • Humans
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscle, Skeletal
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology
  • Muscular Dystrophy, Animal / therapy*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / therapy
  • Oligodeoxyribonucleotides, Antisense / administration & dosage*
  • Oligodeoxyribonucleotides, Antisense / genetics


  • Dystrophin
  • Oligodeoxyribonucleotides, Antisense