Malaria is the most significant vector-borne disease and affects mostly people living in the lesser-developed countries of tropical or sub-tropical regions. Changes in climate, rapid global transportation, immigration and invasion of exotic mosquito vectors bring a threat of introduction of the disease to developed nations. Sustainability of malaria control requires in part the discovery of therapeutic and prophylactic drugs, the development of vaccines, and control of vector mosquitoes. The long-term objective of this application is the production and utilization of strains of vector mosquitoes that are genetically refractory to the transmission of malaria parasites. These insects will be used to test the hypothesis that an increase in the frequency of a gene or allele that confers decreased vector competence to a population of mosquitoes will result in a reduction in the incidence and prevalence of malaria. We propose the development of strains of An. stephensi expressing specific effector molecules that interfere completely with the transmission of the important human malaria parasite, Plasmodium falciparum. To achieve this, the transgenic strains must express effector genes in specific mosquito tissues, the effector gene products must be present in quantities sufficient to disable all parasites, and the gene products must not impose too great a fitness burden.
The SPECIFIC AIMS are to: 1) optimize expression of single-chain antibodies (scFv) that disable Plasmodium falciparum in the midgut and hemolymph of transgenic Anopheles stephensi; 2) construct and test in parasite-challenge assays transgenic An. stephensi carrying single and multiple optimized scFvs for their ability to prevent parasites from infecting midguts and salivary glands; and 3) evaluate the fitness of strains of An. stephensi carrying one or more transgenes expressing antiparasite scFvs relative to control laboratory colonies using life-table parameters. ? ? ?
|Carballar-LejarazÃº, R; Brennock, P; James, A A (2016) Suppressor of hairy-wing, modifier of mdg4 and centrosomal protein of 190 gene orthologues of the gypsy insulator complex in the malaria mosquito, Anopheles stephensi. Insect Mol Biol 25:460-9|
|Kojin, Bianca B; Costa-da-Silva, AndrÃ© Luis; Maciel, Ceres et al. (2016) Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands. Malar J 15:153|
|Peng, Z; Xu, W W; Sham, Y et al. (2016) Mosquito salivary allergen Aed a 3: cloning, comprehensive molecular analysis, and clinical evaluation. Allergy 71:621-8|
|Liu, Hongmei; Liu, Tong; Xie, Lihua et al. (2016) Functional analysis of Orco and odorant receptors in odor recognition in Aedes albopictus. Parasit Vectors 9:363|
|Chen, Xiao-Guang; Jiang, Xuanting; Gu, Jinbao et al. (2015) Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution. Proc Natl Acad Sci U S A 112:E5907-15|
|Gantz, Valentino M; Jasinskiene, Nijole; Tatarenkova, Olga et al. (2015) Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci U S A 112:E6736-43|
|Lo, Eugenia; Yewhalaw, Delenasaw; Zhong, Daibin et al. (2015) Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia. Malar J 14:84|
|Akbari, Omar S; Bellen, Hugo J; Bier, Ethan et al. (2015) BIOSAFETY. Safeguarding gene drive experiments in the laboratory. Science 349:927-9|
|Ling, Lin; Ge, Xie; Li, Zhiqian et al. (2015) MiR-2 family targets awd and fng to regulate wing morphogenesis in Bombyx mori. RNA Biol 12:742-8|
|Alonso-Morales, Alberto; GonzÃ¡lez-LÃ³pez, Lorena; CÃ¡zares-Raga, Febe Elena et al. (2015) Protein phosphorylation during Plasmodium berghei gametogenesis. Exp Parasitol 156:49-60|
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