Source:http://linkedlifedata.com/resource/pubmed/id/21209069
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2011-2-10
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| pubmed:abstractText |
Patients suffering from recessive dystrophic epidermolysis bullosa (RDEB), a hereditary blistering disease of epithelia, show susceptibility to develop highly aggressive squamous cell carcinoma (SCC). Tumors metastasize early and are associated with mortality in the 30th-40th years of life in this patient group. So far, no adequate therapy is available for RDEB SCC. An approach is suicide gene therapy, in which a cell death-inducing agent is introduced to cancer cells. However, lack of specificity has constrained clinical application of this modality. Therefore, we used spliceosome-mediated RNA trans-splicing technology, capable of replacing a tumor-specific transcript with one encoding a cell death-inducing peptide/toxin, to provide tumor-restricted expression. We designed 3' pre-trans-splicing molecules (PTM) and evaluated their efficiency to trans-splice an RDEB SCC-associated target gene, the matrix metalloproteinase-9 (MMP9), in a fluorescence-based test system. A highly efficient PTM was further adapted to insert the toxin streptolysin O (SLO) of Streptococcus pyogenes into the MMP9 gene. Transfection of RDEB SCC cells with the SLO-PTM resulted in cell death and induction of toxin function restricted to RDEB SCC cells. Thus, RNA trans-splicing is a suicide gene therapy approach with increased specificity to treat highly malignant SCC tumors.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1538-8514
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
10
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
233-41
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| pubmed:meshHeading |
pubmed-meshheading:21209069-Bacterial Proteins,
pubmed-meshheading:21209069-Base Sequence,
pubmed-meshheading:21209069-Carcinoma, Squamous Cell,
pubmed-meshheading:21209069-Cell Line,
pubmed-meshheading:21209069-Cell Survival,
pubmed-meshheading:21209069-Epidermolysis Bullosa Dystrophica,
pubmed-meshheading:21209069-Flow Cytometry,
pubmed-meshheading:21209069-Gene Order,
pubmed-meshheading:21209069-Gene Transfer Techniques,
pubmed-meshheading:21209069-Genes, Transgenic, Suicide,
pubmed-meshheading:21209069-HEK293 Cells,
pubmed-meshheading:21209069-Humans,
pubmed-meshheading:21209069-Matrix Metalloproteinase 9,
pubmed-meshheading:21209069-Microscopy, Fluorescence,
pubmed-meshheading:21209069-Molecular Sequence Data,
pubmed-meshheading:21209069-Spliceosomes,
pubmed-meshheading:21209069-Streptolysins,
pubmed-meshheading:21209069-Trans-Splicing
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Spliceosome-mediated RNA trans-splicing facilitates targeted delivery of suicide genes to cancer cells.
|
| pubmed:affiliation |
Division of Molecular Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University, Salzburg, Muellner Hauptstrasse 48, 5020 Salzburg, Austria. c.gruber@salk.at
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|