Invention and Early History of Exon Skipping and Splice Modulation

Methods in Molecular Biology
Kenji Rowel Q Lim, Toshifumi Yokota

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.

Citations

Oct 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Deanna M TiekRebecca B Riggins
Mar 24, 2020·Clinical and Experimental Nephrology·Tomohiko InoueKandai Nozu
Jul 1, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kenji Rowel Q LimToshifumi Yokota
Nov 28, 2018·Journal of Personalized Medicine·Kenji Rowel Q LimToshifumi Yokota
Mar 20, 2021·Frontiers in Genetics·Pedro MoraisYi-Tao Yu
Mar 30, 2021·Frontiers in Pharmacology·Kenji Rowel Q Lim, Toshifumi Yokota

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