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Ligand-mediated retargeting of recombinant adenovirus for gene transfer in vivo

Academic Article
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Overview

authors

  • Thoma, C.
  • Wieland, Stefan
  • Moradpour, D.
  • von Weizsacker, F.
  • Offensperger, S.
  • Madon, J.
  • Blum, H. E.
  • Offensperger, W. B.

publication date

  • June 2000

journal

  • Gene Therapy  Journal

abstract

  • The development of efficient and safe methods for in vivo gene transfer is central to the success of gene therapy. Recombinant adenoviral vectors, although highly efficient, are limited by the host immune response, potential safety hazards due to obligatory cotransfer of viral proteins, and their broad tissue tropism. Here, we demonstrate in an animal model that host range and tissue tropism of a recombinant adenovirus from a distant species can be modified by complexing adenovirus with a cell-specific ligand. Thus, a replication-deficient lacZ recombinant human adenovirus, which naturally does not infect avian cells, allowed highly efficient and specific gene transfer to the liver of ducks in vivo when complexed with N-acetylglucosamine, a ligand for the chicken hepatic lectin. This combination of ligand-mediated receptor targeting with adenoviral uptake and intracellular processing of a given gene represents a novel approach to gene therapy of inherited and acquired liver diseases.

subject areas

  • Acetylglucosamine
  • Adenoviridae
  • Animals
  • Ducks
  • Gene Targeting
  • Gene Transfer Techniques
  • Humans
  • Lectins
  • Ligands
  • Liver
  • Tumor Cells, Cultured
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Research

keywords

  • adenovirus
  • cell-specific gene transfer
  • chicken hepatic lectin
  • liver
  • targeting
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Identity

International Standard Serial Number (ISSN)

  • 0969-7128

Digital Object Identifier (DOI)

  • 10.1038/sj.gt.3301194

PubMed ID

  • 10871753
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Additional Document Info

start page

  • 1039

end page

  • 1045

volume

  • 7

issue

  • 12

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