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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-10-20
pubmed:abstractText
In this study, we evaluated the effect of blood components (whole blood and serum) on asialoglycoprotein receptor-mediated in vivo gene transfer. The hepatic transfection activity of galactosylated lipoplex preincubated with serum was approximately 10 times higher than that without incubation after intraportal injection in mice. However, preincubation with whole blood significantly reduced hepatic transfection activity. Fluorescent resonance energy transfer analysis and agarose gel electrophoresis revealed that preincubation with serum reduced the degree of destabilization of the galactosylated lipoplex in blood, partially supporting enhanced hepatic transfection activity by preincubation with serum. Inhibition of hepatic transfection activity by predosing galactosylated bovine serum albumin indicated that the galactosylated lipoplex exposed to serum is recognized by asialoglycoprotein-receptors on hepatocytes. Inactivation of serum prior to mixing with galactosylated lipoplex reduced liver accumulation and completely abolished enhancement of hepatic transfection activity by preincubation with active serum, suggesting that not only the stability of the lipoplex in blood but also the serum opsonin activity plays important roles. Alternatively, preincubation with inactivated serum reduced the lung accumulation and inflammatory cytokine production of galactosylated lipoplex. The information provided by this study will be valuable for the future use, design, and development of galactosylated lipoplex for in vivo asialoglycoprotein receptor-mediated gene transfer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
484-93
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16033911-Animals, pubmed-meshheading:16033911-Asialoglycoprotein Receptor, pubmed-meshheading:16033911-Blood, pubmed-meshheading:16033911-Cytokines, pubmed-meshheading:16033911-Cytomegalovirus, pubmed-meshheading:16033911-DNA, pubmed-meshheading:16033911-Drug Carriers, pubmed-meshheading:16033911-Female, pubmed-meshheading:16033911-Gene Transfer Techniques, pubmed-meshheading:16033911-Liposomes, pubmed-meshheading:16033911-Liver, pubmed-meshheading:16033911-Luciferases, pubmed-meshheading:16033911-Male, pubmed-meshheading:16033911-Mice, pubmed-meshheading:16033911-Mice, Inbred ICR, pubmed-meshheading:16033911-Plasmids, pubmed-meshheading:16033911-Rats, pubmed-meshheading:16033911-Rats, Wistar, pubmed-meshheading:16033911-Tissue Distribution, pubmed-meshheading:16033911-Transfection
pubmed:year
2005
pubmed:articleTitle
Interaction with blood components plays a crucial role in asialoglycoprotein receptor-mediated in vivo gene transfer by galactosylated lipoplex.
pubmed:affiliation
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't