Antisense-mediated exon inclusion

Hua, Y., Krainer, A. R. (2012) Antisense-mediated exon inclusion. Methods Mol Biol, 867. pp. 307-323. ISSN 1940-6029 (Electronic)1064-3745 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22454070
DOI: 10.1007/978-1-61779-767-5_20

Abstract

Exon skipping induced by gene mutations is a common mechanism responsible for many genetic diseases. A practical approach to correct the aberrant splicing of defective genes is to use antisense oligonucleotides (ASOs). The recognition of splice sites and the regulation of splicing involve multiple positive or negative cis-acting elements and trans-acting factors. Base-pairing of ASOs to a negative element in a targeted pre-mRNA blocks the binding of splicing repressors to this cis-element and/or disrupts an unfavorable secondary structure; as a result, the ASO restores exon inclusion. For example, we have recently shown that appropriate 2'-O-(2-methoxyethyl) (MOE) phosphorothioate-modified ASOs can efficiently correct survival motor neuron 2 (SMN2) exon 7 splicing in a cell-free splicing assay, in cultured human cells-including patient fibroblasts-and in both peripheral tissues and the CNS of SMA mouse models. These ASOs are promising drug leads for SMA therapy.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > antisense
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: 2012
Date Deposited: 30 Jan 2013 20:55
Last Modified: 30 Jan 2013 20:55
PMCID: PMC3390937
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26963

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