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Published online on June 1, 2004, 10.1073/pnas.0402486101
PNAS | June 8, 2004 | vol. 101 | no. 23 | 8676-8681


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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.


Abbreviations: siRNA, short interfering RNA; shRNA, short hairpin RNA; PEI, polyethyleneimine; NP, nucleocapsid protein; MDCK, Madin–Darby canine kidney; PR8, A/Puerto Rico/8/34; RSV, respiratory syncytial virus; i.t., intratracheal; pfu, plaque-forming unit; Luc, luciferase; EGFP, enhanced GFP.

* To whom correspondence should be addressed. E-mail: jchen{at}mit.edu.

© 2004 by The National Academy of Sciences of the USA


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