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.
Available at: http://works.bepress.com/ravindra-singh/37/
This is a post-peer-review, pre-copyedit version of a book chapter published as 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. The final authenticated version is available online at DOI: 10.1007/978-1-4939-8651-4_26. Posted with permission.