795. RNA Interference of Influenza Virus Infection

Top of pageAbstract Influenza A viruses cause epidemics and pandemics in both poultry and humans, inflicting enormous suffering and economical loss. Currently, two strategies, vaccines and small molecule therapeutics, are utilized to control the spread of influenza. Vaccination offers limited protection and requires accurate prediction of future circulating strains and production of sufficient quantities of vaccine for large populations in a short time. There are four antiviral drugs for treatment and/or prophylaxis of influenza. Although the drugs reduce the severity and duration of influenza infections, they have to be administered within the first 24|[ndash]|48 hours after the development of symptoms and can often be associated with side effects. Of greater concern is the emergence of stable and transmissible drug resistant influenza strains. Currently, enormous resources are being devoted to improve the availability of vaccines and antiviral drugs. However, effective control of global influenza pandemics likely requires novel approaches that complement the existing ones. In recent years, RNA interference has emerged as a powerful approach to inhibit virus infection. We have developed short interfering RNAs (siRNAs), specific for conserved regions of influenza viral genome, which are effective against all known human and avian influenza A virus isolates. These siRNAs potently inhibit viral replication in cells, chicken embryos, and mice. The siRNAs are effective in reducing virus titers in the mouse lung when giving either before or after viral infection, or giving either intranasally or intravenously. As siRNAs are negatively charged and do not cross cell membrane, the challenge of siRNA-based medical application is delivery. Development of efficient siRNA delivery systems will require mechanistic studies of pathways by which siRNA/carriers enter, localize and dissociate in cells. Some data shown may be from company that the presentor is a consultant.