Inhibition of influenza virus production in virus-infected mice by RNA interference.
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.
Ge
Qing
Q
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Filip
Lily
L
Bai
Ailin
A
Nguyen
Tam
T
Eisen
Herman N
HN
Chen
Jianzhu
J
D000818:Animals; D005814:Genes, Viral; D005822:Genetic Vectors; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011094:Polyethyleneimine; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014779:Virus Replication
D034741:RNA, Small Interfering; D011094:Polyethyleneimine