Source:http://linkedlifedata.com/resource/pubmed/id/10329021
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1999-7-6
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pubmed:abstractText |
Sindbis virus has been recognized as a potentially useful virus vector for gene therapy. In an effort to improve its utility and provide cell-targeting capability to gene therapy vectors, we recently developed Sindbis virus vectors possessing chimeric envelopes with cell-specific targeting ability [K. Ohno et al. Nature Biotechnol 15:763-767, 1997; K. Sawai et al. Biochem Biophys Res Commun 248:315-323, 1998]. However, a residual problem associated with Sindbis virus vectors is the apoptotic effect of this virus on infected cells. To address this issue, we have studied the possible role of bcl-2 expression. Bcl-2 expression has been postulated to facilitate the establishment of persistent Sindbis viral infection by blocking virus-induced apoptosis. In this study we produced a Sindbis virus vector capable of expressing human bcl-2 and the reporter gene, lacZ. This chimeric virus (SinRep/lacZ/bcl-2/DH-BB) showed a marked reduction in induced apoptosis in infected cells. For example, after infection with this vector, cell proliferation of BHK cells was 55% of that of uninfected cells 2 days after infection and 40% 3 days after infection. While this reflected a significant degree of apoptosis, the effect was much less pronounced than that seen with wild-type Sindbis virus. Cell proliferation was reduced to 26% 2 days after wild-type virus infection of BHK cells and to only 7% 3 days after infection. Although additional work will be required to eliminate apoptosis induced by Sindbis virus vectors, the studies reported here suggest that such a goal may be achievable after additional modification of the vectors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1096-7192
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36-42
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10329021-Animals,
pubmed-meshheading:10329021-Apoptosis,
pubmed-meshheading:10329021-Cell Division,
pubmed-meshheading:10329021-Cell Line,
pubmed-meshheading:10329021-Cricetinae,
pubmed-meshheading:10329021-Genes, Reporter,
pubmed-meshheading:10329021-Genetic Vectors,
pubmed-meshheading:10329021-Immunoblotting,
pubmed-meshheading:10329021-Kidney,
pubmed-meshheading:10329021-Models, Genetic,
pubmed-meshheading:10329021-Plasmids,
pubmed-meshheading:10329021-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10329021-Sindbis Virus,
pubmed-meshheading:10329021-Time Factors,
pubmed-meshheading:10329021-Transcription, Genetic,
pubmed-meshheading:10329021-Transfection,
pubmed-meshheading:10329021-beta-Galactosidase
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pubmed:year |
1999
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pubmed:articleTitle |
Reducing cytotoxicity induced by Sindbis viral vectors.
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pubmed:affiliation |
Department of PathologyKaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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