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rdf:type |
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lifeskim:mentions |
umls-concept:C0001483,
umls-concept:C0007634,
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0086022,
umls-concept:C0185117,
umls-concept:C0205148,
umls-concept:C0205217,
umls-concept:C0282641,
umls-concept:C0442335,
umls-concept:C1274040,
umls-concept:C1450054,
umls-concept:C1550548,
umls-concept:C1555714,
umls-concept:C1705099,
umls-concept:C1705654,
umls-concept:C2911684
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pubmed:issue |
3
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pubmed:dateCreated |
2006-8-14
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pubmed:abstractText |
The present studies investigated the hypothesis that affinity immobilization of replication-defective adenoviruses (Ad) on the surfaces of biodegradable nanoparticles (NP) can improve transduction through uncoupling cellular uptake from the coxsackie-adenovirus receptor (CAR). Ad was tethered to the surfaces of polylactide-based NP that were surface-activated using a photoreactive polyallylamine-benzophenone-pyridyldithiocarboxylate polymer, which enabled (via thiol chemistry) the covalent attachment of Ad-binding proteins, either the recombinant D1 domain of CAR or an adenoviral knob-specific monoclonal antibody. Gene transfer by NP-Ad complexes was studied in relation to cellular uptake as a function of cell type and the character of NP-Ad binding. NP-Ad complexes, but not Ad applied with or without control nonimmune IgG-modified NP, significantly increased green fluorescent protein reporter expression in endothelioma and endothelial and arterial smooth muscle cells (SMC) in direct correlation to the extent of NP-Ad internalization. CAR-independent uptake of NP-Ad was confirmed by demonstrating inhibition of free Ad- but not NP-Ad complex-mediated transduction by knob protein. Complexes formulated with an Ad encoding inducible nitric oxide synthase inhibited growth of cultured SMC to a significantly greater extent than those with (GFP)Ad or (NULL)Ad or free vector. It is concluded that Ad-specific affinity tethering to biodegradable NP can significantly increase the level of gene expression via a CAR-independent uptake mechanism.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1525-0016
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
382-91
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pubmed:dateRevised |
2011-7-1
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pubmed:meshHeading |
pubmed-meshheading:16807119-Adenoviridae,
pubmed-meshheading:16807119-Animals,
pubmed-meshheading:16807119-Antibodies,
pubmed-meshheading:16807119-Arteries,
pubmed-meshheading:16807119-Cell Proliferation,
pubmed-meshheading:16807119-Cells, Cultured,
pubmed-meshheading:16807119-Endocytosis,
pubmed-meshheading:16807119-Gene Expression,
pubmed-meshheading:16807119-Genetic Vectors,
pubmed-meshheading:16807119-Green Fluorescent Proteins,
pubmed-meshheading:16807119-Immunoglobulin G,
pubmed-meshheading:16807119-Myocytes, Smooth Muscle,
pubmed-meshheading:16807119-Nanostructures,
pubmed-meshheading:16807119-Nitric Oxide Synthase Type II,
pubmed-meshheading:16807119-Photochemistry,
pubmed-meshheading:16807119-Polyamines,
pubmed-meshheading:16807119-Polyesters,
pubmed-meshheading:16807119-Rats,
pubmed-meshheading:16807119-Receptors, Virus,
pubmed-meshheading:16807119-Transduction, Genetic,
pubmed-meshheading:16807119-Transgenes
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pubmed:year |
2006
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pubmed:articleTitle |
Adenoviral gene vector tethering to nanoparticle surfaces results in receptor-independent cell entry and increased transgene expression.
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pubmed:affiliation |
Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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