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| |  Approaches to control disease-carrying insects might include suppressing the replication of a virus within mosquitoes to limit their ability to pass it on, or altering the insects’ lifespan so that they die before they can transmit disease.
Dr. Fraser's team is working to develop and test new approaches to suppressing the replication of dengue virus in the cells of its primary vector, Aedes aegypti mosquitoes. The team is using genetic strategies to introduce a molecular mechanism that uses the dengue virus' own genetic make-up to initiate a process that results in the death of infected cells in the mosquitoes, limiting their ability to transmit disease. In addition, investigators are working on tools to enhance the application of this and other genetic strategies in mosquitoes. |
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| | | Develop genetic constructs to be carried in the mosquito genome, which produce transcription products that will be incorporated into the viral RNA genome (Group I intron trans-splicing ribozymes) within an infected cell. These will be designed to recognize conserved sequences shared by all dengue virus genomes and to carry the gene for a toxin that will kill the infected cell. These molecules will be tested for their ability to suppress virus infection of mosquito cells. | | | | | Develop a system to select for mosquitoes with these anti-Dengue genetic constructs. | | | | | Develop methods for stable, irreversible, and targeted introduction of genes within the Aedes aegypti genome. | | |
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| | | Constructing and testing several Group I introns that attack a conserved sequence of the dengue virus genome. These introns were effective in recognizing, cutting, and splicing sequence to an artificial dengue virus RNA sequence at the specified target site. | | | | | Using transient transfection assays to demonstrate effective recognition and splicing of the Group I introns to infect viral genomes in insect cells. | | | | | Inducing effective cell death in insect cell lines and identifying effective intergenic IRES that operate in mosquito cells. | | | | | The project team is selecting transformed cell lines that express their Group I introns to analyze their effectiveness in splicing as constitutively expressed gene products They will continue testing of this approach in dengue virus infected mosquito cell lines, and possibly intact mosquitoes. | | |
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| | | Dr Stephen Higgs, University of Texas, Medical Branch, Texas, United States - US | | |
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