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

Overview

MeSH Major

  • Adenoviruses, Human
  • Gene Transfer Techniques
  • Genetic Vectors
  • Kupffer Cells
  • Liver

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.

publication date

  • January 1997

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC191093

PubMed ID

  • 8985392

Additional Document Info

start page

  • 624

end page

  • 9

volume

  • 71

number

  • 1