Source:http://linkedlifedata.com/resource/pubmed/id/17375065
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-5-18
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| pubmed:abstractText |
Monoclonal antibody (mAb) delivery by gene transfer in vivo may be an attractive alternative to current mAb therapies for applications that require long-term therapy. This article describes a transfer system that allows inducible high-level expression of unmodified mAbs in vivo. A recombinant adeno-associated viral (rAAV) vector is used that comprises an expression cassette consisting of a dimerizer-regulated promoter that drives expression of the antibody heavy and light chains linked by a 2A self-processing peptide and a furin cleavage site. Following intravenous injection of the rAAV vector, serum mAb levels >1 mg/ml were attained by administration of the inducer, rapamycin. Antibody expression could be rapidly shut off by discontinuing treatment with rapamycin. By optimizing the furin cleavage sequence, this system generated native antibody in vivo, decreasing the likelihood of a host immune response to foreign sequences. In summary, this optimized mAb expression system allows regulated high-level expression of native full-length mAbs in vivo and may offer a new opportunity for delivery of therapeutic mAbs in the clinic.
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| 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 |
Jun
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| pubmed:issn |
1525-0016
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
15
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1153-9
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| pubmed:meshHeading |
pubmed-meshheading:17375065-Amino Acid Sequence,
pubmed-meshheading:17375065-Animals,
pubmed-meshheading:17375065-Antibodies, Monoclonal,
pubmed-meshheading:17375065-Binding Sites,
pubmed-meshheading:17375065-Blotting, Western,
pubmed-meshheading:17375065-CHO Cells,
pubmed-meshheading:17375065-Cell Line,
pubmed-meshheading:17375065-Cricetinae,
pubmed-meshheading:17375065-Cricetulus,
pubmed-meshheading:17375065-Dependovirus,
pubmed-meshheading:17375065-Dose-Response Relationship, Drug,
pubmed-meshheading:17375065-Drug Delivery Systems,
pubmed-meshheading:17375065-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:17375065-Female,
pubmed-meshheading:17375065-Furin,
pubmed-meshheading:17375065-Gene Expression,
pubmed-meshheading:17375065-Genetic Vectors,
pubmed-meshheading:17375065-Humans,
pubmed-meshheading:17375065-Immunoglobulin Heavy Chains,
pubmed-meshheading:17375065-Mass Spectrometry,
pubmed-meshheading:17375065-Mice,
pubmed-meshheading:17375065-Mice, Inbred C57BL,
pubmed-meshheading:17375065-Mice, Nude,
pubmed-meshheading:17375065-Molecular Sequence Data,
pubmed-meshheading:17375065-Sirolimus
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| pubmed:year |
2007
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| pubmed:articleTitle |
An antibody delivery system for regulated expression of therapeutic levels of monoclonal antibodies in vivo.
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| pubmed:affiliation |
Department of Preclinical Oncology and Immunology, Cell Genesys, Inc., South San Francisco, California 94080, USA. Jianminf@cellgenesys.com
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| pubmed:publicationType |
Journal Article
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