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Polycation-mediated delivery of siRNAs for prophylaxis and treatment of influenza virus infection

Influenza A virus causes one of the most prevalent infections in humans. In a typical year, 10 – 20% of the population of the US is infected by influenza virus, resulting in up to 40,000 deaths and 200,000 hospitalisations. Vaccination is the most effective preventative measure that can protect 70 – 90% of healthy adults aged < 65; however, the protection rate is much lower in those most susceptible to infection, namely infants, the elderly and individuals with weakened immune systems. Although four drugs have been approved by the FDA for use as prophylaxis and/or treatment of influenza, concerns about their side effects and the emergence of drug-resistant viruses persist. RNA interference (RNAi), an emerging method of post transcriptional gene silencing, appears ideal for the prevention and treatment of influenza. RNAi in mammals can be mediated by short interfering RNAs (siRNAs) of ∼21– 27 nucleotides in length. The authors have previously shown that si-RNAs specific for conserved regions of the influenza virus genome are potent inhibitors of influenza virus replication in both cell lines and chicken embryos. This review discusses the recent progress in the invivo inhibition of influenza virus by the delivery of siRNAs mediated by non-viral vectors, and the prospects of this strategy for prophylaxis and treatment of influenza infection in humans.