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Exon Skipping and Inclusion Therapies pp 3–30Cite as

Invention and Early History of Exon Skipping and Splice Modulation

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

Abstract

Since its discovery in 1977, much has been known about RNA splicing and how it plays a central role in human development, function, and, notably, disease. Defects in RNA splicing account for at least 10% of all genetic disorders, with the number expected to increase as more information is uncovered on the contribution of noncoding genomic regions to disease. Splice modulation through the use of antisense oligonucleotides (AOs) has emerged as a promising avenue for the treatment of these disorders. In fact, two splice-switching AOs have recently obtained approval from the US Food and Drug Administration: eteplirsen (Exondys 51) for Duchenne muscular dystrophy, and nusinersen (Spinraza) for spinal muscular atrophy. These work by exon skipping and exon inclusion, respectively. In this chapter, we discuss the early development of AO-based splice modulation therapy—its invention, first applications, and its evolution into the approach we are now familiar with. We give a more extensive history of exon skipping in particular, as it is the splice modulation approach given the most focus in this book.

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Kenji Rowel Q. Lim & Toshifumi Yokota

  2. The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, AB, Canada

    Toshifumi Yokota

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  1. Kenji Rowel Q. Lim
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  2. Toshifumi Yokota
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Correspondence to Toshifumi Yokota .

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  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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Lim, K.R.Q., Yokota, T. (2018). Invention and Early History of Exon Skipping and Splice Modulation. 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_1

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