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2. Development of interfering RNA agents to inhibit SARS associated coronavirus infection and replication
 
Funds : Research Fund for the Control of Infectious Diseases (investigator-initiated projects)
Project Status : Closed
Reference No. : 01030152
Project Title : Development of interfering RNA agents to inhibit SARS associated coronavirus infection and replication
Applicant(s) : He ML(1)
Zheng B(2)
Kung HF(1)
Affiliation(s) : The Institute of Molecular Biology, The University of Hong Kong(1)

Department of Microbiology, The University of Hong Kong(2)

Approved Amount (HK$) : $804,572.00
Abstract : Severe acute respiratory syndrome (SARS) recently emerged as a human disease associated with pneumonia. The virus spread to more than 30 countries and caused disease in more than 8100 patients across five continents, including Hong Kong this year. A novel coronavirus (SCoV) was identified as the etiological agent of SARS, and the virus causes a similar disease in cynomolgous macaques. We have developed siRNAs targeting on the conserved replicase 1A region, which blocked SCoV infection and replication (He et al, JAMA, in press). Although the precise functions of other four structure genes (S, E, M, and N) have not been well characterized, it is proposed that they are important for host cell entry and virion morphogenesis and release. All the four structural genes have unique roles in the structure, infection and replication of the SARS-CoV. Therefore, we propose that they are also potentially good targets for gene silencing by siRNAs. Furthermore, since these siRNAs are targeting different SARS genes, when combined together, they would have synergistic effects. Here we propose (1) to design more siRNAs to knock-down the four structural genes and test their effects in the inhibition of SARS infection and replication in vitro in the monkey kidney (FRhk-4 cells) cell culture system; (2) to test the potential combinational synergistic anti-viral effects of different siRNA; (3) to test the potential synergistic effect of siRNA in combination with other known therapeutic agents; and (4) to develop recombinant Adenovirus (rAd) gene delivery system for the expression of shRNAs to combat SARS coronavirus infection.
Keywords : Anti-virus, RNA interference, recombinant Adenovirus, rAd-shRNA, gene therapy, SARS-Co virus, siRNA
Instruments :
Remarks :



Dissemination Report : [PDF file]
01030152dr.pdf


Final Report : [PDF file]
01030152fr.pdf

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Last revision date: 15 August 2006