tetano
Editor, Senior Moderator
J Virol. 2012 Jul 11. [Epub ahead of print]
5' triphosphate-siRNA: potent inhibition of influenza A virus infection by gene silencing and RIG-I activation.
Lin L, Liu Q, Berube N, Detmer S, Zhou Y.
Source
Vaccine and Infectious Disease Organization.
Abstract
Limited protection of current vaccines and antiviral drugs against influenza A virus infection underscores the urgent need for development of novel anti-influenza virus interventions. While short interfering RNA (siRNA) has been shown to be able to inhibit influenza virus infection in a gene specific manner, activation of retinoic acid-inducible gene I protein (RIG-I) pathway has an anti-viral effect in a gene non-specific mode. In this study, we designed and tested the anti-influenza virus effect of a short double stranded RNA, designated 3p-mNP1496-siRNA that possesses dual functions: a siRNA targeting influenza NP gene and an agonist for RIG-I activation. This double stranded siRNA possesses a triphosphate group at the 5' end of the sense strand and is blunt ended. Our study showed that 3p-mNP1496-siRNA could potently inhibit influenza A virus infection both in cell culture and in mice. The strong inhibition effect was attributed to its siRNA function as well as its ability to activate RIG-I pathway. To the best of our knowledge, this is the first report that the combination of siRNA together with RIG-I pathway activation can synergistically inhibit influenza A virus infection. The development of such dual functional RNA molecules will greatly contribute to the arsenal of tools to combat not only influenza viruses but also other important viral pathogens.
PMID:
22787226
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22787226
5' triphosphate-siRNA: potent inhibition of influenza A virus infection by gene silencing and RIG-I activation.
Lin L, Liu Q, Berube N, Detmer S, Zhou Y.
Source
Vaccine and Infectious Disease Organization.
Abstract
Limited protection of current vaccines and antiviral drugs against influenza A virus infection underscores the urgent need for development of novel anti-influenza virus interventions. While short interfering RNA (siRNA) has been shown to be able to inhibit influenza virus infection in a gene specific manner, activation of retinoic acid-inducible gene I protein (RIG-I) pathway has an anti-viral effect in a gene non-specific mode. In this study, we designed and tested the anti-influenza virus effect of a short double stranded RNA, designated 3p-mNP1496-siRNA that possesses dual functions: a siRNA targeting influenza NP gene and an agonist for RIG-I activation. This double stranded siRNA possesses a triphosphate group at the 5' end of the sense strand and is blunt ended. Our study showed that 3p-mNP1496-siRNA could potently inhibit influenza A virus infection both in cell culture and in mice. The strong inhibition effect was attributed to its siRNA function as well as its ability to activate RIG-I pathway. To the best of our knowledge, this is the first report that the combination of siRNA together with RIG-I pathway activation can synergistically inhibit influenza A virus infection. The development of such dual functional RNA molecules will greatly contribute to the arsenal of tools to combat not only influenza viruses but also other important viral pathogens.
PMID:
22787226
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22787226