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

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• 作者：Weidong Zhang (1)
  Rajeswari Singam (1)
  Gary Hellermann (1)
  Xiaoyuan Kong (1)
  Homero San Juan (1)
  Richard F Lockey (1)
  Shuen-Ju Wu (2)
  Kevin Porter (2)
  Shyam S Mohapatra (1)
  
• 关键词：dengue virus ; siRNA ; gene expression ; adeno ; associated virus
• 刊名：Genetic Vaccines and Therapy
• 出版年：2004
• 出版时间：December 2004
• 年：2004
• 卷：2
• 期：1
• 全文大小：788KB
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• 作者单位：Weidong Zhang (1)
  Rajeswari Singam (1)
  Gary Hellermann (1)
  Xiaoyuan Kong (1)
  Homero San Juan (1)
  Richard F Lockey (1)
  Shuen-Ju Wu (2)
  Kevin Porter (2)
  Shyam S Mohapatra (1)
  
  1. Division of Allergy and Immunology-JMC Airway Disease Research Center, Department of Internal Medicine, University of South Florida, VA Hospital, Tampa, FL, USA
  2. Viral Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA
  
• ISSN：1479-0556

文摘

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.