Source:http://linkedlifedata.com/resource/pubmed/id/18180775
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2008-2-25
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| pubmed:abstractText |
A unifying characteristic of prion diseases is the conversion of a normal cellular protein (PrP(c)) to an abnormal pathogenic conformation, designated PrP(sc). Antibodies directed against PrP(c), when added to scrapie-infected cell cultures or passively administered in vivo, can result in elimination of PrP(sc) or prevent its replication, respectively. In our efforts to develop an approach with potential prophylactic utility we employed a recombinant adeno-associated vector type 2 (rAAV2) viral vector platform to express PrP(c)-specific single-chain fragment variable (scFv) antibodies within the central nervous system (CNS) of susceptible mice that were subsequently inoculated peripherally with infectious prions. Vector expressed scFvs delayed onset of prion pathogenesis as evidenced by improvements in clinical signs and rotarod performance, in extended incubation periods, and in decreased PrP(sc) burden in the CNS. This novel antibody delivery platform enables the in vivo translation of prion prophylactics to other species afflicted by transmissible spongiform encephalopathies (TSEs) and which also has relevance to the development of therapeutics for other protein-misfolding diseases such as Alzheimer's or Parkinson's disease.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1525-0024
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
481-6
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| pubmed:meshHeading |
pubmed-meshheading:18180775-Amino Acid Sequence,
pubmed-meshheading:18180775-Animals,
pubmed-meshheading:18180775-Antibodies,
pubmed-meshheading:18180775-Blotting, Western,
pubmed-meshheading:18180775-Cell Line,
pubmed-meshheading:18180775-Central Nervous System,
pubmed-meshheading:18180775-Densitometry,
pubmed-meshheading:18180775-Dependovirus,
pubmed-meshheading:18180775-Endopeptidase K,
pubmed-meshheading:18180775-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18180775-Genetic Vectors,
pubmed-meshheading:18180775-Humans,
pubmed-meshheading:18180775-Immunoblotting,
pubmed-meshheading:18180775-Immunohistochemistry,
pubmed-meshheading:18180775-Immunoprecipitation,
pubmed-meshheading:18180775-Mice,
pubmed-meshheading:18180775-Molecular Sequence Data,
pubmed-meshheading:18180775-PrPC Proteins,
pubmed-meshheading:18180775-Prion Diseases,
pubmed-meshheading:18180775-Sequence Homology, Amino Acid,
pubmed-meshheading:18180775-Surface Plasmon Resonance,
pubmed-meshheading:18180775-Transduction, Genetic
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
CNS delivery of vectored prion-specific single-chain antibodies delays disease onset.
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| pubmed:affiliation |
Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|