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Redirecting adenovirus to pulmonary endothelium by cationic liposomes

Academic Article
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Overview

authors

  • Ma, Z.
  • Mi, Z.
  • Wilson, A.
  • Alber, S.
  • Robbins, Paul D.
  • Watkins, S.
  • Pitt, B.
  • Li, S.

publication date

  • February 2002

journal

  • Gene Therapy  Journal

abstract

  • Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route.

subject areas

  • Adenoviridae
  • Animals
  • Endothelium, Vascular
  • Fatty Acids, Monounsaturated
  • Female
  • Gene Expression
  • Genetic Therapy
  • Genetic Vectors
  • Liposomes
  • Liver
  • Lung
  • Lung Diseases
  • Mice
  • Mice, Inbred Strains
  • Muscle, Smooth, Vascular
  • Quaternary Ammonium Compounds
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Research

keywords

  • adenovirus
  • gene therapy
  • liposome
  • pulmonary endothelium
  • targeting
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Identity

International Standard Serial Number (ISSN)

  • 0969-7128

Digital Object Identifier (DOI)

  • 10.1038/sj/gt/3301636

PubMed ID

  • 11859420
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Additional Document Info

start page

  • 176

end page

  • 182

volume

  • 9

issue

  • 3

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