Inhibition of respiratory viruses by nasally administered siRNA.
Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are two respiratory pathogens of paramount medical significance that exert high mortality. At present, there is no reliable vaccine or antiviral drug against either virus. Using an RNA interference (RNAi) approach, we show that individual as well as joint infection by RSV and PIV can be specifically prevented and inhibited by short interfering RNAs (siRNAs), instilled intranasally in the mouse, with or without transfection reagents. The degree of protection matched the antiviral activity of the siRNA in cell culture, allowing an avenue for quick screening of an efficacious siRNA. When targeting both viruses in a joint infection, excess of one siRNA moderated the inhibitory effect of the other, suggesting competition for the RNAi machinery. Our results suggest that, if properly designed, low dosages of inhaled siRNA might offer a fast, potent and easily administrable antiviral regimen against respiratory viral diseases in humans.
Bitko
Vira
V
Department of Biochemistry and Molecular Biology (MSB 2370), University of South Alabama, College of Medicine, 307 University Boulevard, Mobile, Alabama 36688-0002, USA.
Musiyenko
Alla
A
Shulyayeva
Olena
O
Barik
Sailen
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D007372:Interferons / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D018108:Respirovirus / Q000187:drug effects*
D000998:Antiviral Agents; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007372:Interferons