title: Antisense methods to modulate pre-mRNA splicing.
abstract: The dynamic process of pre-mRNA splicing is regulated by combinatorial control exerted by overlapping cis-elements that are unique to every exon and its flanking intronic sequences. Splicing cis-elements are usually 4-8-nucleotide-long linear motifs that furnish interaction sites for specific proteins. Secondary and higher-order RNA structures exert an additional layer of control by providing accessibility to cis-elements. Antisense oligonucleotides (ASOs) that block splicing cis-elements and/or affect RNA structure have been shown to modulate alternative splicing in vivo. Consistently, ASO-based strategies have emerged as a powerful tool for therapeutic manipulation of aberrant splicing in pathological conditions. Here we describe the application of an ASO-based approach for the enhanced production of the full-length mRNA of SMN2 in spinal muscular atrophy patient cells.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Joonbae
authors.initials: J
authors.lastname: Seo
authors.forename: Eric W
authors.initials: EW
authors.lastname: Ottesen
authors.forename: Ravindra N
authors.initials: RN
authors.lastname: Singh
mesh_terms: D006801:Humans; D007438:Introns; D008967:Molecular Biology / Q000379:methods*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology; D020320:Oligoribonucleotides, Antisense / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics* / Q000648:ultrastructure; D012326:RNA Splicing / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D020320:Oligoribonucleotides, Antisense; D012322:RNA Precursors; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein