Linked Life Data

17567471

Source:http://linkedlifedata.com/resource/pubmed/id/17567471

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-6-14
pubmed:abstractText
Altered gene expression in liver sinusoidal endothelial cells (SEC) is associated with a variety of aspects of liver pathophysiology. It is, therefore, possible to envision a new therapeutic strategy for treatment of intractable liver diseases and achievement of graft-specific immunotolerance through modulation of SEC functions by genetic engineering. The SEC possesses unique hyaluronan receptors that recognize and internalize hyaluronic acid (HA). This characteristic was used in the development of a system for targeting foreign DNA to SEC. A gene carrier system was prepared by coupling HA oligomers to poly L-lysine (PLL) in a 1:1 weight ratio by reductive amination reaction. The resulting copolymer (PLL-g-HA) was mixed with various amounts of DNA in 154 mM NaCl. Inter-polyelectrolyte complex formation between PLL-g-HA and DNA exhibited minimal self-aggregation, explaining the highly soluble nature of the complex. Complex formation between PLL-g-HA and DNA was further assessed with a gel retardation assay. The titration point representing the minimum proportion of PLL-g-HA required to retard the DNA completely occurred at a 1:1 copolymer (based on PLL) to DNA charge ratio. Following intravenous injection of (32)P-labeled pSV beta-Gal plasmid complexed to PLL-g-HA in Wistar rats, >90% of the injected counts were shown to be taken up by the liver. Further, it was shown that the PLL-g-HA/DNA complex was distributed exclusively in the SEC. At 72 h after injection of 90 mug of pSV beta-Gal in a PLL-g-HA-complexed form, a large number of SEC expressing beta-galactosidase were detected. So, the PLL-g-HA/DNA system permits targeted delivery of exogenous nucleotide agents selectively to the liver SEC, providing a novel strategy for manipulation of SEC functions.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0815-9319
pubmed:author
pubmed:issnType
Print
pubmed:volume
22 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S68-72
pubmed:dateRevised
2010-6-9
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Genetic manipulation of sinusoidal endothelial cells.
pubmed:affiliation
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. ytakei@med.juntendo.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't