Evaluation of Cell-Penetrating Peptide Delivery of Antisense Oligonucleotides for Therapeutic Efficacy in Spinal Muscular Atrophy

  • Suzan M. HammondEmail author
  • Frank Abendroth
  • Michael J. Gait
  • Matthew J. A. Wood
Part of the Methods in Molecular Biology book series (MIMB, volume 2036)


Antisense oligonucleotides (ASOs) are a widely used form of gene therapy, which is translatable to multiple disorders. A major obstacle for ASO efficacy is its bioavailability for in vivo and in vitro studies. To overcome this challenge we use cell-penetrating peptides (CPPs) for systemic delivery of ASOs. One of the most advanced clinical uses of ASOs is for the treatment of spinal muscular atrophy (SMA). In this chapter, we describe the techniques used for in vitro screening and analysing in vivo biodistribution of CPP-conjugated ASOs targeting the survival motor neuron 2, SMN2, the dose-dependent modifying gene for SMA.

Key words

Cell-penetrating peptides Oligonucleotide delivery Spinal muscular atrophy Survival motor neuron Splice switching oligonucleotides 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Suzan M. Hammond
    • 1
    Email author
  • Frank Abendroth
    • 2
    • 3
  • Michael J. Gait
    • 2
  • Matthew J. A. Wood
    • 1
  1. 1.Department of PaediatricsUniversity of OxfordOxfordUK
  2. 2.Laboratory of Molecular BiologyMedical Research CouncilCambridgeUK
  3. 3.Institute of Pharmacy and BiochemistryJohannes Gutenberg-University of MainzMainzGermany

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