James A McSwiggen1, Shaguna Seth. 1. Nastech Pharmaceutical Company, Inc., 3830 Monte Villa Parkway, Bothell, WA 98021-7266, USA. jmcswiggen@nastech.com
Abstract
BACKGROUND: The recent emergence of avian H5N1 influenza virus has led to a growing concern regarding the potential for another influenza pandemic on the scale of the 1918 - 1919 outbreaks. Current influenza vaccines and therapies are effective against seasonal flu, but may prove inadequate in a flu pandemic due to influenza's propensity for rapid mutation and re-assortment. RNA interference (RNAi) therapies offer the potential of a new therapeutic approach, by targeting conserved regions of the influenza viral genome. OBJECTIVE: To evaluate RNAi as a potential mode of treatment for pandemic influenza. METHODS: The review describes current therapies and compares them to potential RNAi therapeutics, with emphasis on the potential hurdles facing RNAi therapeutics in the areas of drug design, delivery, treatment regimen and viral escape. CONCLUSIONS: RNAi therapeutics targeting > 95% of known influenza A sequences, including the avian H5N1 strains, have been shown to be highly effective in vitro. The challenge ahead will be to find effective delivery modalities that achieve the same high degree of effectiveness in human subjects and at an affordable cost. Viral escape will continue to be a concern until new RNAi therapeutics demonstrate that they can overcome, or at least minimize, this phenomenon.
BACKGROUND: The recent emergence of avian H5N1influenza virus has led to a growing concern regarding the potential for another influenza pandemic on the scale of the 1918 - 1919 outbreaks. Current influenza vaccines and therapies are effective against seasonal flu, but may prove inadequate in a flu pandemic due to influenza's propensity for rapid mutation and re-assortment. RNA interference (RNAi) therapies offer the potential of a new therapeutic approach, by targeting conserved regions of the influenza viral genome. OBJECTIVE: To evaluate RNAi as a potential mode of treatment for pandemic influenza. METHODS: The review describes current therapies and compares them to potential RNAi therapeutics, with emphasis on the potential hurdles facing RNAi therapeutics in the areas of drug design, delivery, treatment regimen and viral escape. CONCLUSIONS: RNAi therapeutics targeting > 95% of known influenza A sequences, including the avian H5N1 strains, have been shown to be highly effective in vitro. The challenge ahead will be to find effective delivery modalities that achieve the same high degree of effectiveness in human subjects and at an affordable cost. Viral escape will continue to be a concern until new RNAi therapeutics demonstrate that they can overcome, or at least minimize, this phenomenon.