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. 1994 Jan 4;91(1):215–219. doi: 10.1073/pnas.91.1.215

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

J Kolls 1, K Peppel 1, M Silva 1, B Beutler 1
PMCID: PMC42917  PMID: 8278368

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.

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Selected References

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