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Exon Skipping pp 117–129Cite as

Overview on AON Design

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 867))

Abstract

Antisense-mediated exon skipping is an attractive tool to study gene function as well as a promising therapeutic application for a number of diseases. In order for antisense oligonucleotides (AONs) to induce effective exon skipping during pre-mRNA splicing, they have to fulfill certain criteria. These include resistance against endo- and exonucleases and RNase H-induced cleavage and suitable thermodynamic properties. Furthermore, the AON-target sequence needs to be accessible and should contain sequence motives that are essential for proper inclusion of the exon into the mRNA. For most genes, only a few AONs have been designed, with the exception of the DMD gene, for which over 400 AONs targeting the majority of DMD exons have been reported. This allows retrospective analysis of effective and ineffective AONs to obtain guidelines to optimize future AON design.

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Acknowledgments

Willeke van Roon and Mark Einderhand are acknowledged for proofreading the manuscript and helpful comments and suggestions. The author receives funding from ZonMw (the Netherlands), the Dutch Duchenne Parent Project (the Netherlands), Spieren voor spieren (Prinses Beatrix Foundation, the Netherlands), and the European Union (LUMC is partner in the TREAT-NMD network of excellence (LSHM-CT-2006-036825) and the BIO-NMD project (HEALTH-F2-2009-241665)). The LUMC participates in the Center for Biomedical Genetics (the Netherlands) and the Center for Medical Systems Biology (the Netherlands).

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Authors and Affiliations

  1. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Annemieke Aartsma-Rus

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  1. Annemieke Aartsma-Rus
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Correspondence to Annemieke Aartsma-Rus .

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Editors and Affiliations

  1. Dept. Human & Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, Leiden, 2333 ZC, Netherlands

    Annemieke Aartsma-Rus

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Aartsma-Rus, A. (2012). Overview on AON Design. In: Aartsma-Rus, A. (eds) Exon Skipping. Methods in Molecular Biology, vol 867. Humana Press. https://doi.org/10.1007/978-1-61779-767-5_8

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  • DOI: https://doi.org/10.1007/978-1-61779-767-5_8

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-766-8

  • Online ISBN: 978-1-61779-767-5

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