| pubmed-article:15353044 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0521026 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0017296 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0035696 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0013682 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0600448 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0086022 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C1554184 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C1549479 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C1705099 | lld:lifeskim |
| pubmed-article:15353044 | lifeskim:mentions | umls-concept:C0442335 | lld:lifeskim |
| pubmed-article:15353044 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:15353044 | pubmed:dateCreated | 2004-9-8 | lld:pubmed |
| pubmed-article:15353044 | pubmed:abstractText | Therapeutic application of recombinant adeno-associated virus (AAV) has been limited by its small carrying capacity. To overcome this limitation trans-splicing vectors were developed recently. However, the transduction efficiency of trans-splicing vectors is considerably lower than that of a single intact vector in skeletal muscle. To improve trans-splicing vectors for skeletal muscle gene therapy, we examined whether coinfection efficiency is a rate-limiting factor in the mdx mouse, a model for Duchenne muscular dystrophy. Two different AAV viruses were delivered to the mdx muscle. Similar to previous reports in normal muscle, coinfection efficiency reached approximately 90% in the diseased muscle. This result suggests that coinfection is not a hurdle in dystrophic muscle. Another critical step in the trans-splicing method is the transcription and splicing across the inverted terminal repeat (ITR) junction in the reconstituted genome. To test whether this represented a significant obstacle, we systematically evaluated the transcription, pre-mRNA stability and splicing, and translation in a synthetic lacZ construct that mimicked the reconstituted genome. Although inserting an intron in the lacZ gene had no effect on its expression, inclusion of the ITR junction in the intron reduced expression by 50%. In construct containing the ITR junction, the mRNA transcript level was significantly reduced. This mRNA level reduction was associated with decreased pre-mRNA stability. These data suggest that the accumulation of mRNA is a rate-limiting factor in trans-splicing vector-mediated gene therapy. | lld:pubmed |
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| pubmed-article:15353044 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15353044 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15353044 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15353044 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15353044 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:15353044 | pubmed:issn | 1043-0342 | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:JayFF | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:DuanDongsheng... | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:PintelDavid... | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:QiuJianmingJ | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:YueYongpingY | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:XuZhupingZ | lld:pubmed |
| pubmed-article:15353044 | pubmed:author | pubmed-author:YeChaoyangC | lld:pubmed |
| pubmed-article:15353044 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15353044 | pubmed:volume | 15 | lld:pubmed |
| pubmed-article:15353044 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15353044 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15353044 | pubmed:pagination | 896-905 | lld:pubmed |
| pubmed-article:15353044 | pubmed:dateRevised | 2011-4-20 | lld:pubmed |
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| pubmed-article:15353044 | pubmed:meshHeading | pubmed-meshheading:15353044... | lld:pubmed |
| pubmed-article:15353044 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15353044 | pubmed:articleTitle | Trans-splicing adeno-associated viral vector-mediated gene therapy is limited by the accumulation of spliced mRNA but not by dual vector coinfection efficiency. | lld:pubmed |
| pubmed-article:15353044 | pubmed:affiliation | Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA. | lld:pubmed |
| pubmed-article:15353044 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15353044 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15353044 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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