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Attenuation of Dengue Virus Infection by Adeno-Associated Virus- Mediated siRNA Delivery

机译:通过腺相关病毒介导的siRNa递送衰减登革热病毒感染

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Background: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Results: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAV- mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.

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