Source:http://linkedlifedata.com/resource/pubmed/id/10678358
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2000-2-29
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| pubmed:abstractText |
Tumor-directed gene therapy, such as "suicide gene" therapy, requires high levels of gene expression in a high percentage of tumor cells in vivo to be effective. Current vector strategies have been ineffective in achieving these goals. This report introduces the attenuated (thymidine kinase (TK)-negative) replication-competent vaccinia virus (VV) as a potential vector for tumor-directed gene therapy by studying the biodistribution of VV in animal tumor models. A TK-deleted recombinant VV (Western Reserve strain) expressing luciferase on a synthetic promoter was constructed. Luciferase activity was measured in vitro after transduction of a variety of human and murine tumor cell lines and in vivo after intraperitoneal (i.p.) delivery in C57BL/6 mice with 7-day i.p. tumors (10(6) MC-38 cells). Three other in vivo tumor models were examined for tumor-specific gene expression after intravenous delivery of VV (human melanoma in nude mice, adenocarcinoma liver metastasis in immunocompetent mice, and subcutaneous sarcoma in the rat). In addition, a replication-incompetent vaccinia (1 microg of psoralen and ultraviolet light, 365 nm, 4 minutes) was tested in vitro and in vivo and compared with active virus. Luciferase activity in i.p. tumors at 4 days after i.p. injection of VV was >7000-fold higher than lung, >3000-fold higher than liver, and >250-fold higher than ovary. In addition, intravenous injection of VV resulted in markedly higher tumor luciferase activity compared with any other organ in every model tested (up to 188,000-fold higher than liver and 77,000-fold higher than lung). Inactivation of the virus resulted in negligible gene expression in vivo. In summary, VV has a high transduction efficiency in tumor cells with high levels of gene expression. The results suggest a selective in vivo replication of TK-deleted VV in tumor cells. Replication competent, TK-deleted VV appears to be an ideal vector for testing the in vivo delivery of toxic genes to tumor cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ficusin,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Photosensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0929-1903
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
7
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
66-73
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| pubmed:dateRevised |
2006-4-21
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| pubmed:meshHeading |
pubmed-meshheading:10678358-Animals,
pubmed-meshheading:10678358-Disease Models, Animal,
pubmed-meshheading:10678358-Ficusin,
pubmed-meshheading:10678358-Gene Expression,
pubmed-meshheading:10678358-Gene Therapy,
pubmed-meshheading:10678358-Genetic Vectors,
pubmed-meshheading:10678358-HT29 Cells,
pubmed-meshheading:10678358-Humans,
pubmed-meshheading:10678358-Luciferases,
pubmed-meshheading:10678358-Mice,
pubmed-meshheading:10678358-Mice, Inbred C57BL,
pubmed-meshheading:10678358-Mice, Nude,
pubmed-meshheading:10678358-Mutation,
pubmed-meshheading:10678358-Neoplasms, Experimental,
pubmed-meshheading:10678358-Photosensitizing Agents,
pubmed-meshheading:10678358-Rats,
pubmed-meshheading:10678358-Rats, Inbred F344,
pubmed-meshheading:10678358-Thymidine Kinase,
pubmed-meshheading:10678358-Transfection,
pubmed-meshheading:10678358-Tumor Cells, Cultured,
pubmed-meshheading:10678358-Tumor Markers, Biological,
pubmed-meshheading:10678358-Ultraviolet Rays,
pubmed-meshheading:10678358-Vaccinia virus,
pubmed-meshheading:10678358-Virus Replication
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| pubmed:year |
2000
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| pubmed:articleTitle |
Vaccinia as a vector for tumor-directed gene therapy: biodistribution of a thymidine kinase-deleted mutant.
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| pubmed:affiliation |
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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| pubmed:publicationType |
Journal Article
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