Hua, Y., Krainer, A. R. (2012) Antisense-mediated exon inclusion. Methods Mol Biol, 867. pp. 307-323. ISSN 1940-6029 (Electronic)1064-3745 (Linking)
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: | https://repository.cshl.edu/id/eprint/26963 |
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