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Title: Lipid emulsions potently increase transgene expression in hepatocytes after adenoviral transfer
Authors: Snoeys, Jan ×
Mertens, Geertrui
Lievens, Joke
van Berkel, Theo
Collen, Desire
Biessen, Erik A L
De Geest, Bart #
Issue Date: Jan-2006
Publisher: Academic Press
Series Title: Molecular Therapy vol:13 issue:1 pages:98-107
Abstract: Elimination of Kupffer cells by cytotoxic clodronate liposomes increases transgene expression in the liver after adenoviral transfer. Here, we demonstrate that empty l-alpha-phosphatidylcholine liposomes block uptake of vectors in the reticuloendothelial cells of the liver and increase human apolipoprotein (apo) A-I (approved gene symbol apo A-I) expression in C57BL/6 (1.3-fold) and Balb/c mice (3.1-fold) to the same extent as clodronate liposomes (1.5- and 3.4-fold, respectively). A similar elevation of human apo A-I levels was induced by the lipid emulsion Intralipid (1.5- and 2.8-fold in C57BL/6 and Balb/c mice, respectively). Not only Kupffer cells but also hepatic sinusoidal endothelial cells (HSEC) constitute the reticuloendothelial cells of the liver. The uptake of adenoviral vectors 1 h after transfer in C57BL/6 mice was 2.9-fold lower in Kupffer cells than in HSEC. In contrast, Kupffer cell uptake in Balb/c mice was 2.6-fold higher than in HSEC. Vector uptake in reticuloendothelial cells of the liver was reduced and transgene expression was increased in splenectomized and Rag2-deficient Balb/c mice but not in splenectomized and Rag1-deficient C57BL/6 mice. In conclusion, lipid emulsions for parenteral clinical use block uptake of adenoviral vectors by the reticuloendothelial cells of the liver and potently increase transgene expression.
URI: 
ISSN: 1525-0016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Leuven Language Institute (ILT)
Division of Geology
× corresponding author
# (joint) last author

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