Source:http://linkedlifedata.com/resource/pubmed/id/16763664
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
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| pubmed:dateCreated |
2006-10-17
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| pubmed:abstractText |
We recently reported a novel coupling strategy involving salicylhydroxamic acid and phenyl(di)boronic acid molecules to attach the CNGRC peptide to PEI/DNA for CD13 targeting in tumors. Here, we doubly coupled Simian Virus (SV) 40 peptide-(nuclear localization signal)) and oligonucleotide-based (DNA nuclear targeting signal) nuclear signals to the same vector using peptide nucleic acid chemistry. This vector, CNGRC/PEG/PEI/DNA-betagal/NLS/DNTS, was predominantly localized in the cell nucleus, yielding about 200-fold higher betagal gene expression in vitro, more than 20-fold increase in tumor-specific gene delivery, and a robust betagal gene expression as demonstrated in stained tumor sections. For gene therapy purposes, we further engineered a similar targeting polyplex, CNGRC/PEG/PEI/DNA-p53/NLS/DNTS, with EBV-based episomal vector for sustained p53 gene expression. A distribution of vector DNA and apoptosis in p53-containing tumors was observed, yielding a significant tumor regression and 95% animal survival after 60 days. This multicomponent vector also co-targeted tumor and tumor-associated endothelial cells but not normal cells, and had more efficient therapeutic index than each vector administered as a single modality. The use of an efficient coupling strategy without compromising the vector's integrity for DNA condensation and endosomal escape; nuclear import; tumor-specific and persistent p53 gene expression clearly provides a basis for developing a single combinatorial approach for non-viral gene therapy.
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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 |
Nov
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| pubmed:issn |
0969-7128
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
13
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1512-23
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| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:16763664-Animals,
pubmed-meshheading:16763664-Antigens, CD13,
pubmed-meshheading:16763664-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:16763664-Cations,
pubmed-meshheading:16763664-Cell Line, Tumor,
pubmed-meshheading:16763664-Cell Proliferation,
pubmed-meshheading:16763664-DNA,
pubmed-meshheading:16763664-Gene Expression,
pubmed-meshheading:16763664-Gene Targeting,
pubmed-meshheading:16763664-Gene Therapy,
pubmed-meshheading:16763664-Genes, p53,
pubmed-meshheading:16763664-Genetic Engineering,
pubmed-meshheading:16763664-Genetic Vectors,
pubmed-meshheading:16763664-Humans,
pubmed-meshheading:16763664-Immunohistochemistry,
pubmed-meshheading:16763664-In Situ Nick-End Labeling,
pubmed-meshheading:16763664-Lung Neoplasms,
pubmed-meshheading:16763664-Mice,
pubmed-meshheading:16763664-Mice, Nude,
pubmed-meshheading:16763664-Neoplasm Transplantation,
pubmed-meshheading:16763664-Polyethyleneimine,
pubmed-meshheading:16763664-Simian virus 40,
pubmed-meshheading:16763664-Transfection
|
| pubmed:year |
2006
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| pubmed:articleTitle |
A multifunctional PEI-based cationic polyplex for enhanced systemic p53-mediated gene therapy.
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| pubmed:affiliation |
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. stanley-moffatt@excite.com
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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