| pubmed-article:20861136 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20861136 | lifeskim:mentions | umls-concept:C0079298 | lld:lifeskim |
| pubmed-article:20861136 | lifeskim:mentions | umls-concept:C0035696 | lld:lifeskim |
| pubmed-article:20861136 | lifeskim:mentions | umls-concept:C1416717 | lld:lifeskim |
| pubmed-article:20861136 | lifeskim:mentions | umls-concept:C1527180 | lld:lifeskim |
| pubmed-article:20861136 | pubmed:issue | 23 | lld:pubmed |
| pubmed-article:20861136 | pubmed:dateCreated | 2010-11-5 | lld:pubmed |
| pubmed-article:20861136 | pubmed:abstractText | The major challenge to a successful gene therapy of autosomal dominant genetic diseases is a highly efficient and specific knock-down or repair of the disease-causing allele. In epidermolysis bullosa simplex-type Dowling-Meara (EBS-DM), a single amino acid exchange in exon 1 of the keratin 14 gene (K14) triggers a severe skin phenotype, characterized by blistering of the skin and mucous membranes after minor trauma. We chose spliceosome-mediated RNA trans-splicing to specifically replace exons 1-7 of the K14 gene. In this approach, the mutated coding region is replaced by an RNA-trans-splicing molecule (RTM) that incorporates a binding domain (BD) and the wild-type sequence of K14. Since the BD is crucial for the trans-splicing functionality, we developed a fluorescence-based RTM screen consisting of an RTM library containing random BDs. Co-transfection of the library with a target molecule enabled us to identify highly functional RTMs. The best RTMs were adapted for endogenous trans-splicing in an EBS-DM patient cell line. In this cell line, we were able to detect functional, efficient and correct trans-splicing on RNA and protein levels. Scratch assays confirmed phenotypic reversion in vitro. Owing to concomitant knock-down and repair of the mutated allele, we assume that trans-splicing is a promising tool for the treatment of autosomal dominant genetic disease. | lld:pubmed |
| pubmed-article:20861136 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20861136 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20861136 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20861136 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20861136 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20861136 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20861136 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:20861136 | pubmed:issn | 1460-2083 | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:WagnerMartinM | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:HintnerHelmut... | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:BauerJohann... | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:KollerUlrichU | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:WallyVerenaV | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:TrostAndreaA | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:LettnerThomas... | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:BrunnerMariet... | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:MurauerEva... | lld:pubmed |
| pubmed-article:20861136 | pubmed:author | pubmed-author:HainzlStefanS | lld:pubmed |
| pubmed-article:20861136 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20861136 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:20861136 | pubmed:volume | 19 | lld:pubmed |
| pubmed-article:20861136 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20861136 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20861136 | pubmed:pagination | 4715-25 | lld:pubmed |
| pubmed-article:20861136 | pubmed:meshHeading | pubmed-meshheading:20861136... | lld:pubmed |
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| pubmed-article:20861136 | pubmed:meshHeading | pubmed-meshheading:20861136... | lld:pubmed |
| pubmed-article:20861136 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20861136 | pubmed:articleTitle | K14 mRNA reprogramming for dominant epidermolysis bullosa simplex. | lld:pubmed |
| pubmed-article:20861136 | pubmed:affiliation | Division of Molecular Dermatology and EB-house Austria, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria. | lld:pubmed |
| pubmed-article:20861136 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20861136 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
