Precision guided SIT for the control of vector-borne disease
精准引导昆虫不育技术用于控制媒介传播疾病
基本信息
- 批准号:10087886
- 负责人:
- 金额:$ 46.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-23 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAedesAllelesAutomobile DrivingBiological AssayBiologyCRISPR/Cas technologyCandidate Disease GeneContractsCulicidaeDataDengueDengue FeverDevelopmentDisease VectorsDrosophila melanogasterEmbryoEngineeringEnsureEntomologyEnvironmentEssential GenesEvaluationExhibitsFemaleFertilityFertility StudyFrequenciesGene TargetingGenerationsGenesGeneticGenetic VectorsGenomeGoldGuide RNAHomingInfectionInfection preventionInsectaKnock-outLeadLegalLifeLocationMalariaMale SterilityMasculineMechanicsMethodsMosaicismMosquito ControlOrganismPharmaceutical PreparationsPhenotypePopulationPopulation ControlPopulation GeneticsProductionReproducibilityRiskSeriesSiteSterilitySystemTechnologyTransgenesTransgenic OrganismsVaccinesVector-transmitted infectious diseaseWolbachiaWorkYellow FeverZIKAbasecombinatorialcomparative genomicscostcost effectivedesigndisorder preventioneggendonucleaseexperimental studyfitnessfunctional genomicsimprovedinnovationinsightloss of functionmalemale fertilitymathematical modelnew technologynoveloffspringpreventprogramsscreeningsexsex determinationsexual dimorphismsterile insect techniquesuccesstechnology/techniquetooltranscriptomicstransgene expressionvectorvector controlvector mosquitozika fever
项目摘要
PROJECT SUMMARY
Billions of people are at risk of contracting vector-borne diseases. Dengue alone causes 90 million infections
per year globally and like many vector-borne diseases, currently there are no drugs or vaccines to treat or prevent
these infections. Therefore, vector control is the primary tool used for vector-borne disease prevention. In
recent years, novel vector population suppression technologies have been created (e.g. RIDL and Wolbachia
based systems), but production of mosquitoes for these programs is labor intensive and is limited in scalability
and distribution. In this study, we will use a functional genomic screening approach to identify key sex
determinate, female essential (FE) and male fertility (MF) genes in the dengue vector, Ae. aegypti. These studies
will improve our understanding of the biology of this important vector and it can be used to inform the design of
new genetic population suppression methods to control this vector. After these genes are identified and
characterized, we will incorporate them into the design of precision guided sterile insect technique (pgSIT)
technologies in an attempt to overcome limitations in traditional SIT control strategies. Sterile insect technique
(SIT) is the gold standard for insect population control but has many limitations. Our proposed technology aims
to simultaneously knock-out FE and MF genes using a binary CRISPR/Cas9 system in the Ae. aegypti disease
vector. One line will target one or more female essential FE genes and one or more MF genes and the other
line will express a Cas9. When these two lines are crossed, they create sterile, male progeny that are ready for
release into a population suppression program. To generate these lines, initially we will characterize >40
candidate FE and MF genes A. aegypti in single and combinatorial sgRNA screening assays in our previously
characterized Cas9 expression. These genes will be initially selected through transcriptomics, comparative
genomics and functional genomic studies. Gene targets that exhibit consistent FE or MF phenotypes will then
be engineered into transgenic Ae. aegypti line expressing guide RNAs (gRNA) targeting these genes. These
lines will then be crossed to multiple Cas9 lines and the fitness of each line and their F1 progeny will be
determined over many generations to ensure population stability. The design and integration of these
transgenes will then be varied and optimized to facilitate improved, stable and consistent phenotypes. These
optimization experiments will also address multiple fundamental questions about lethal biallelic mosaicism, a
phenomenon identified as driving pgSIT success in D. melanogaster, and endogenous Cas9 expression
systems, including the impact of transgene expression timing and transgene location on the long-term stability
of the lines. The optimal design and genes will then be evaluated in fitness and small population cage studies.
In the end, we aim to identify novel FE and MF genes that will allow us to better understand mosquito biology
and which allow us to create a genetic SIT system that improves upon traditional SIT technologies.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Omar Sultan Akbari其他文献
Omar Sultan Akbari的其他文献
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{{ truncateString('Omar Sultan Akbari', 18)}}的其他基金
Development of precision genome editing tools in Ae. albopictus for functional genetics and mosquito control technologies
开发 Ae 中的精确基因组编辑工具。
- 批准号:
10362718 - 财政年份:2021
- 资助金额:
$ 46.12万 - 项目类别:
The olfactory basis of locating nectar sugar sources in Aedes aegypti mosquitoes
埃及伊蚊定位花蜜糖源的嗅觉基础
- 批准号:
10802906 - 财政年份:2021
- 资助金额:
$ 46.12万 - 项目类别:
The olfactory basis of locating nectar sugar sources in Aedes aegypti mosquitoes
埃及伊蚊定位花蜜糖源的嗅觉基础
- 批准号:
10366069 - 财政年份:2021
- 资助金额:
$ 46.12万 - 项目类别:
The olfactory basis of locating nectar sugar sources in Aedes aegypti mosquitoes
埃及伊蚊定位花蜜糖源的嗅觉基础
- 批准号:
10207040 - 财政年份:2021
- 资助金额:
$ 46.12万 - 项目类别:
The olfactory basis of locating nectar sugar sources in Aedes aegypti mosquitoes
埃及伊蚊定位花蜜糖源的嗅觉基础
- 批准号:
10582687 - 财政年份:2021
- 资助金额:
$ 46.12万 - 项目类别:
Precision guided SIT for the control of vector-borne disease
精准引导昆虫不育技术用于控制媒介传播疾病
- 批准号:
10326334 - 财政年份:2020
- 资助金额:
$ 46.12万 - 项目类别:
Precision guided SIT for the control of vector-borne disease
精准引导昆虫不育技术用于控制媒介传播疾病
- 批准号:
10533815 - 财政年份:2020
- 资助金额:
$ 46.12万 - 项目类别:
Development of synthetic gene drives using small molecules
使用小分子开发合成基因驱动器
- 批准号:
10470220 - 财政年份:2019
- 资助金额:
$ 46.12万 - 项目类别:
Development of synthetic gene drives using small molecules
使用小分子开发合成基因驱动器
- 批准号:
10254421 - 财政年份:2019
- 资助金额:
$ 46.12万 - 项目类别:
Developing reciprocal chromosomal translocations for wild population replacement in an important vector of human disease.
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- 批准号:
9243803 - 财政年份:2016
- 资助金额:
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