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

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Oligonucleotide-Based Therapies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2036))

Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Paediatrics, University of Oxford, Oxford, UK

    Suzan M. Hammond & Matthew J. A. Wood

  2. Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK

    Frank Abendroth & Michael J. Gait

  3. Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudingerweg 5, D-55128, Mainz, Germany

    Frank Abendroth

Authors
  1. Suzan M. Hammond
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  2. Frank Abendroth
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  3. Michael J. Gait
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  4. Matthew J. A. Wood
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Corresponding author

Correspondence to Suzan M. Hammond .

Editor information

Editors and Affiliations

  1. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Olof Gissberg

  2. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Rula Zain

  3. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Karin E. Lundin

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Hammond, S.M., Abendroth, F., Gait, M.J., Wood, M.J.A. (2019). Evaluation of Cell-Penetrating Peptide Delivery of Antisense Oligonucleotides for Therapeutic Efficacy in Spinal Muscular Atrophy. In: Gissberg, O., Zain, R., Lundin, K. (eds) Oligonucleotide-Based Therapies. Methods in Molecular Biology, vol 2036. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9670-4_13

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  • DOI: https://doi.org/10.1007/978-1-4939-9670-4_13

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9669-8

  • Online ISBN: 978-1-4939-9670-4

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