Attenuation of Dengue Virus Infection by Adeno-Associated Virus-Mediated siRNA Delivery
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 09, 2004
- Accession Number
- ADA447952
Entities
People
- Gary Hellermann
- Homero S. Juan
- Kevin Porter
- Rajeswari Singam
- Richard F. Lockey
- Shuen-ju Wu
- Shyam S> Mohapatra
- Weidong Zhang
- Xiaoyuan Kong
Organizations
- University of South Florida