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

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Abstract ral ss BioMed CentGenetic Vaccines and Therapy Open AcceResearch Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery Weidong Zhang1, Rajeswari Singam1, Gary Hellermann1, Xiaoyuan Kong1, Homero San Juan1, Richard F Lockey1, Shuen-Ju Wu2, Kevin Porter2 and Shyam S Mohapatra*1 Address: 1Division of Allergy and Immunology-JMC Airway Disease Research Center, Department of Internal Medicine, University of South Florida; VA Hospital Tampa, FL, USA and 2Viral Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA Email: Weidong Zhang - [email protected]; Rajeswari Singam - [email protected]; Gary Hellermann - [email protected]; Xiaoyuan Kong - [email protected]; Homero San Juan - [email protected]; Richard F Lockey - [email protected]; Shuen- Ju Wu - [email protected]; Kevin Porter - [email protected]; Shyam S Mohapatra* - [email protected] * Corresponding author dengue virussiRNAgene expressionadeno-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 DE

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