Nonsequential Pre-mRNA Splicing: From Basic Understanding to Impacts on Splice-Manipulating Therapies

Kristin A. Ham, Steve D. Wilton, May T. Aung-Htut

Research output: Chapter in Book/Conference paperChapterpeer-review

Abstract

The pre-mRNA splicing process is an essential aspect of gene expression and function and plays a substantial role in the complexity of higher eukaryotes. The development of antisense oligonucleotides (AOs) to harness the splicing process and manipulate it to treat various inherited and acquired diseases has been boosted by its flexibility and customisation capability. As the amount of research in this space increases, certain aspects need to be considered, in particular, how nonsequential splicing of pre-mRNA can impact AO-mediated splicing manipulation. In this chapter, we reviewed literature discussing intron removal order and several examples of disease-causing mutations impacted by this phenomenon. We also compared two strategies used to study intron removal order and the occasions that they are best suited. Finally, we discuss how nonsequential splicing could facilitate or impede the development of splice-manipulating AOs and aspects to consider when analysing AO effectiveness.
Original languageEnglish
Title of host publicationMessenger RNA Therapeutics
EditorsStefan Jurga, Jan Barciszewski
Place of PublicationSwitzerland
PublisherSpringer Science + Business Media
Pages429-446
Number of pages18
Volume13
ISBN (Electronic)9783031084157
ISBN (Print)9783031084140
DOIs
Publication statusPublished - 2022

Publication series

NameRNA Technologies
Volume13
ISSN (Print)2197-9731
ISSN (Electronic)2197-9758

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