[Protection against lethal influenza virus challenge by RNA interference in vivo ]
>>Published online before print June 1, 2004
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0402630101
Medical Sciences
Protection against lethal influenza virus challenge by RNA interference in vivo
Stephen Mark Tompkins *, Chia-Yun Lo *, Terrence M. Tumpey , and Suzanne L. Epstein *
*Laboratory of Immunology and Developmental Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; and Influenza Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333
Communicated by Herman N. Eisen, Massachusetts Institute of Technology, Cambridge, MA, April 13, 2004 (received for review March 18, 2003)
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.<<
>>Published online before print June 1, 2004
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0402486101
Medical Sciences
Inhibition of influenza virus production in virus-infected mice by RNA interference
Qing Ge, Lily Filip, Ailin Bai, Tam Nguyen, Herman N. Eisen, and Jianzhu Chen *
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139
Contributed by Herman N. Eisen, April 9, 2004
Influenza A virus infection is a major source of morbidity and mortality worldwide. Because the effectiveness of existing vaccines and antiviral drugs is limited, development of new treatment modalities is needed. Here, we show that short interfering RNAs (siRNAs) specific for conserved regions of influenza virus genes can prevent and treat influenza virus infection in mice. Virus production in lungs of infected mice is reduced by siRNAs given either before or after initiating virus infection, by using slow i.v. administration of small volumes containing siRNAs in complexes with a polycation carrier. Similar effects also are observed when mice are given DNA vectors i.v. or intranasally, from which siRNA precursors can be transcribed. Development of delivery systems that may be compatible with human use demonstrates the potential utility of siRNAs for prophylaxis and therapy of influenza virus infections in humans.<<
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