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

J. Kolls, K. Peppel, M. Silva, B. Beutler

Research output: Contribution to journalArticle

206 Scopus citations

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 109 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 β-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.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number1
DOIs
StatePublished - Jan 4 1994

ASJC Scopus subject areas

  • General

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