CPP-Directed Oligonucleotide Exon Skipping in Animal Models of Duchenne Muscular Dystrophy

  • HaiFang Yin
  • Hong Moulton
  • Corinne Betts
  • Matthew Wood
Part of the Methods in Molecular Biology book series (MIMB, volume 683)


Antisense oligonucleotides (AOs) are effective splice switching agents and have potential as therapeutics via the exclusion or inclusion of specific target gene exons to ameliorate and modify disease progression. The leading example is Duchenne muscular dystrophy (DMD), a fatal muscle degenerative disease, where AO-mediated skipping of specific DMD gene exons can restore the disrupted DMD open reading frame, leading to the production of functional dystrophin protein and ameliorate the DMD phenotype in animal models. Clinical proof-of-concept has recently been shown in two successful, independent Phase I clinical trials. These trials both followed local intramuscular treatments, and the challenge now is to develop and test systemic protocols, which will be required for treatment-aimed disease modification. Recently, a number of groups have demonstrated the promise of AOs directly conjugated to cell-penetrating peptides (CPPs) as having significant potential for systemic delivery and therapeutic correction in DMD animal models. Here, we review the background to this work and describe in detail the experimental protocols used in studies aimed at investigating CPP-conjugated AOs as systemic splice correcting agents in animal models of DMD.

Key words

Antisense oligonucleotide Morpholino Cell-penetrating peptide Splice correction Exon skipping Duchenne muscular dystrophy Dystrophin Muscle Heart Systemic delivery 



This work was supported by UK Department of Health and the UK Muscular Dystrophy Campaign. The authors would like to thank the UK MDEX Consortium for helpful discussions and support. They would also like to thank Professor Kay Davies, Department of Physiology, Anatomy and Genetics, University of Oxford for providing access to facilities including the mdx mouse colony.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • HaiFang Yin
    • 1
  • Hong Moulton
    • 2
  • Corinne Betts
    • 3
  • Matthew Wood
    • 1
  1. 1.Anatomy and Genetics, Department of PhysiologyUniversity of OxfordOxfordUK
  2. 2.Oregon State UniversityCorvallisUSA
  3. 3.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK

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