Inhibition of influenza virus production in virus-infected mice by RNA interference

• DOI: 10.1073/pnas.0402486101
• Publication Date: 2004-06-02T00:53:24Z
• Authors: Qing Ge; Lily Filip; Ailin Bai; Tam Nguyen; Herman N. Eisen; Jianzhu Chen
• Keywords: Male; 0301 basic medicine; Genes, Viral; Genetic Vectors; Virus Replication; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Influenza A virus; Influenza, Human; Injections, Intravenous; Animals; Humans; Polyethyleneimine; RNA Interference; RNA, Small Interfering

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.