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Pre-mRNA Splicing Modulation by Antisense Oligonucleotides

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Exon Skipping and Inclusion Therapies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1828))

Abstract

Pre-mRNA splicing, a dynamic process of intron removal and exon joining, is governed by a combinatorial control exerted by overlapping cis-elements that are unique to each exon and its flanking intronic sequences. Splicing cis-elements are usually 4-to-8-nucleotide-long linear motifs that provide binding sites for specific proteins. Pre-mRNA splicing is also influenced by secondary and higher order RNA structures that affect accessibility of splicing cis-elements. Antisense oligonucleotides (ASOs) that block splicing cis-elements and/or affect RNA structure have been shown to modulate splicing in vivo. Therefore, ASO-based strategies have emerged as a powerful tool for therapeutic manipulation of splicing in pathological conditions. Here we describe an ASO-based approach to increase the production of the full-length SMN2 mRNA in spinal muscular atrophy patient cells.

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Acknowledgments

This work was supported by grants from US National Institutes of Health (R01 NS055925, R21 NS101312) and Salsbury Endowment (Iowa State University, Ames, IA, USA) to R.N.S.

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Natalia N. Singh, Diou Luo & Ravindra N. Singh

Authors
  1. Natalia N. Singh
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  2. Diou Luo
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  3. Ravindra N. Singh
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Corresponding author

Correspondence to Natalia N. Singh .

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Editors and Affiliations

  1. Medical Genetics, University of Alberta, Edmonton, AB, Canada

    Toshifumi Yokota

  2. Medical Genetics, University of Alberta, Edmonton, AB, Canada

    Rika Maruyama

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Singh, N.N., Luo, D., Singh, R.N. (2018). Pre-mRNA Splicing Modulation by Antisense Oligonucleotides. In: Yokota, T., Maruyama, R. (eds) Exon Skipping and Inclusion Therapies. Methods in Molecular Biology, vol 1828. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8651-4_26

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  • DOI: https://doi.org/10.1007/978-1-4939-8651-4_26

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8650-7

  • Online ISBN: 978-1-4939-8651-4

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