Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ

Item Type:	Article
Title:	Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ
Creators Name:	Wolff, G. and Worgall, S. and van Rooijen, N. and Song, W.R. and Harvey, B.G. and Crystal, R.G.
Abstract:	Based on the hypothesis that tissue macrophages present an obstacle for adenovirus (Ad) vector-mediated gene transfer to internal organs, this study evaluated the consequences of transient depletion of Kupffer cells on subsequent transfer of the Ad vector genome and Ad vector-directed gene expression in the livers of experimental animals. Depletion of Kupffer cells in mice by intravenous administration of multilamellar liposomes containing dichloromethylene-bisphosphonate permitted subsequent intravenous administration of an Ad vector to provide a higher input of recombinant adenoviral DNA to the liver, an absolute increase in transgene expression, and a delayed clearance of the vector DNA and transgene expression. These observations suggest that the tissue macrophages pose a significant hurdle to Ad vector-mediated gene transfer and that strategies to transiently suppress macrophage defenses might be useful in enhancing the efficiency of this in vivo gene transfer system.
Keywords:	Human Adenoviruses, Gene Expression, Gene Transfer Techniques, Genetic Vectors, Kupffer Cells, Liver, Transgenes, Animals, Mice
Source:	Journal of Virology
ISSN:	0022-538X
Volume:	71
Number:	1
Page Range:	624-629
Date:	1 January 1997
Official Publication:	http://jvi.asm.org/cgi/content/abstract/71/1/624
PubMed:	View item in PubMed

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