Source:http://linkedlifedata.com/resource/pubmed/id/17551501
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2007-7-24
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| pubmed:abstractText |
Spinal muscular atrophy (SMA) is caused by loss of survival motor neuron-1 (SMN1). A nearly identical copy gene called SMN2 is present in all SMA patients; however SMN2 produces low levels of functional protein due to alternative splicing. Recently a therapeutic approach has been developed referred to as trans-splicing. Conceptually, this strategy relies upon pre-messenger RNA (pre-mRNA) splicing occurring between two separate molecules: (i) the endogenous target RNA and (ii) the therapeutic RNA that provides the correct RNA sequence via a trans-splicing event. SMN trans-splicing RNAs were initially examined and expressed from a plasmid-backbone and shown to re-direct splicing from a SMN2 mini-gene as well as from endogenous transcripts. Subsequently, recombinant adeno-associated viral vectors were developed that expressed and delivered trans-splicing RNAs to SMA patient fibroblasts. In the severe SMA patient fibroblasts, SMN2 splicing was redirected via trans-splicing to produce increased levels of full-length SMN mRNA and total SMN protein levels. Finally, small nuclear ribonucleoprotein (snRNP) assembly, a critical function of SMN, was restored to SMN-deficient SMA fibroblasts following treatment with the trans-splicing vector. Together these results demonstrate that the alternatively spliced SMN2 exon 7 is a tractable target for replacement by trans-splicing.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMN Complex Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMN2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Survival of Motor Neuron 1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Survival of Motor Neuron 2 Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
|
| pubmed:issn |
1525-0016
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1471-8
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17551501-Alternative Splicing,
pubmed-meshheading:17551501-Base Sequence,
pubmed-meshheading:17551501-Cell Line,
pubmed-meshheading:17551501-Cell Survival,
pubmed-meshheading:17551501-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:17551501-Fibroblasts,
pubmed-meshheading:17551501-Gene Transfer Techniques,
pubmed-meshheading:17551501-Humans,
pubmed-meshheading:17551501-Molecular Sequence Data,
pubmed-meshheading:17551501-Muscular Atrophy, Spinal,
pubmed-meshheading:17551501-Nerve Tissue Proteins,
pubmed-meshheading:17551501-RNA, Messenger,
pubmed-meshheading:17551501-RNA-Binding Proteins,
pubmed-meshheading:17551501-SMN Complex Proteins,
pubmed-meshheading:17551501-Survival of Motor Neuron 1 Protein,
pubmed-meshheading:17551501-Survival of Motor Neuron 2 Protein,
pubmed-meshheading:17551501-Trans-Splicing,
pubmed-meshheading:17551501-Transcription, Genetic
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| pubmed:year |
2007
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| pubmed:articleTitle |
Restoration of SMN function: delivery of a trans-splicing RNA re-directs SMN2 pre-mRNA splicing.
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| pubmed:affiliation |
Department of Veterinary Pathobiology, Bond Life Sciences Center, University of Missouri, Columbia, Missouri 65211-7310, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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