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

  • ️Sat Jan 01 1994

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

J Kolls et al. Proc Natl Acad Sci U S A. 1994.

Erratum in

  • Proc Natl Acad Sci U S A 1994 Mar 1;91(5):1979

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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