Source:http://linkedlifedata.com/resource/pubmed/id/11506697
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2001-8-16
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| pubmed:abstractText |
The skin offers a tissue site accessible for delivery of gene-based therapeutics. To develop the capability for sustained systemic polypeptide delivery via cutaneous gene transfer, we generated and injected pseudotyped HIV-1 lentiviral vectors intradermally at a range of doses into human skin grafted on immune-deficient mice. Unlike Moloney murine leukemia virus (MLV)-based retrovectors, which failed to achieve detectable cutaneous gene transfer by this approach, lentivectors effectively targeted all major cell types within human skin tissue, including fibroblasts, endothelial cells, keratinocytes, and macrophages. After a single injection, lentivectors encoding human erythropoietin (EPO) produced dose-dependent increases in serum human EPO levels and hematocrit that increased rapidly within one month and remained stable subsequently. Delivered gene expression was confined locally at the injection site. Excision of engineered skin led to rapid and complete loss of human EPO in the bloodstream, confirming that systemic EPO delivery was entirely due to lentiviral targeting of cells within skin rather than via spread of the injected vector to visceral tissues. These findings indicate that the skin can sustain dosed systemic delivery of therapeutic polypeptides via direct lentivector injection and thus provide an accessible and reversible approach for gene-based delivery to the bloodstream.
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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 |
Aug
|
| pubmed:issn |
1043-0342
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
10
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| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1551-8
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11506697-Animals,
pubmed-meshheading:11506697-Cells, Cultured,
pubmed-meshheading:11506697-Dose-Response Relationship, Drug,
pubmed-meshheading:11506697-Endothelium,
pubmed-meshheading:11506697-Erythropoietin,
pubmed-meshheading:11506697-Fibroblasts,
pubmed-meshheading:11506697-Gene Transfer Techniques,
pubmed-meshheading:11506697-Genetic Vectors,
pubmed-meshheading:11506697-Hematocrit,
pubmed-meshheading:11506697-Humans,
pubmed-meshheading:11506697-Keratinocytes,
pubmed-meshheading:11506697-Lentivirus,
pubmed-meshheading:11506697-Macrophages,
pubmed-meshheading:11506697-Mice,
pubmed-meshheading:11506697-Mice, SCID,
pubmed-meshheading:11506697-Peptides,
pubmed-meshheading:11506697-Skin,
pubmed-meshheading:11506697-Time Factors
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
Sustainable systemic delivery via a single injection of lentivirus into human skin tissue.
|
| pubmed:affiliation |
Veterans Affairs Palo Alto Healcare System and Program in Epithelial Biology, Stanford University School of Medicine, CA 94305, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|