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Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer

Academic Article
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Overview

authors

  • Kolls, J.
  • Peppel, K.
  • Silva, M.
  • Beutler, Bruce

publication date

  • 1994

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • A chimeric protein capable of binding and neutralizing tumor necrosis factor (TNF) and lymphotoxin was expressed in mice transduced with a replication-incompetent adenoviral vector into which a TNF inhibitor gene had been engineered. Within 3 days following the injection of 10(9) infectious particles, the TNF inhibitor concentration exceeded 1 mg/ml of plasma; this level of expression was maintained for at least 4 weeks, and detectable TNF inhibitory activity was measured 6 weeks after injection of the recombinant virus. Introduction of the artificial gene produced a phenotypic effect comparable to homozygous deletion of the 55-kDa TNF receptor, in that animals were rendered highly susceptible to infection by Listeria monocytogenes, whereas control animals receiving a replication-incompetent virus coding for beta-galactosidase were capable of resisting Listeria challenge. Adenovirus-mediated transfer of a gene encoding a TNF inhibitor offers a practical means of imposing effective, long-term blockade of TNF activity in vivo for investigational and therapeutic purposes.

subject areas

  • Adenoviridae
  • Animals
  • Gene Transfer Techniques
  • Immunoglobulin G
  • Listeriosis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
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Identity

PubMed Central ID

  • PMC42917

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.91.1.215

PubMed ID

  • 8278368
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Additional Document Info

start page

  • 215

end page

  • 219

volume

  • 91

issue

  • 1

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