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Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

Author(s): Zhang Weidong | Singam Rajeswari | Hellermann Gary | Kong Xiaoyuan | Juan Homero | Lockey Richard | Wu Shuen-Ju | Porter Kevin | Mohapatra Shyam

Journal: Genetic Vaccines and Therapy
ISSN 1479-0556

Volume: 2;
Issue: 1;
Start page: 8;
Date: 2004;
Original page

Keywords: dengue virus | siRNA | gene expression | adeno-associated virus

Abstract 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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