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Proc Natl Acad Sci U S A 2004 Jun 8;101(23):8682-6

Protection against lethal influenza virus challenge by RNA interference in vivo.

Tompkins SM, Lo CY, Tumpey TM, Epstein SL

Epstein SL, US FDA, Lab Immunol & Dev Biol, Div Cellular & Gene Therapies, Off Cell Tissue & Gene Therapies,Ctr Biol & Evalu, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Dev Biol, Div Cell & Gene Therapies, Bethesda, MD 20892 USA Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Influenza Branch, Atlanta, GA 30333 USA


Influenza virus infection is responsible for hundreds of thousands of deaths annually. Current vaccination strategies and antiviral drugs provide limited protection; therefore, new strategies are needed. RNA interference is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with small interfering RNAs (siRNAs) specific for highly conserved regions of the nucleoprotein or acidic polymerase inhibits influenza A virus replication in vivo. Delivery of these siRNAs significantly reduced lung virus titers in infected mice and protected animals from lethal challenge. This protection was specific and not mediated by an antiviral IFN response. Moreover, influenza-specific siRNA treatment was broadly effective and protected animals against lethal challenge with highly pathogenic avian influenza A viruses of the H5 and H7 subtypes. These results indicate that RNA interference is promising for control of influenza virus infection, as well as other viral infections.

Category: Journal Article, Peer
PubMed ID: #15173583
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29