Development of tools for site-directed analysis of gene function
基因功能定点分析工具的开发
基本信息
- 批准号:10580007
- 负责人:
- 金额:$ 76.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-06-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AllelesAnimal ModelAnimalsAwardBindingCRISPR/Cas technologyCellsClinicCollaborationsCommunitiesCustomDNADNA Double Strand BreakDNA IntegrationDataDevelopmentDiseaseDoctor of PhilosophyEducational workshopEmbryoFeedbackFishesGene ExpressionGene MutationGenesGenomeGenome engineeringGenomicsGoalsGrantGuide RNAHealthHealth PromotionHumanHybridsIntronsIowaKnock-inLaboratoriesLearningMediatingMethodologyMethodsMicroinjectionsModelingModificationMutationOnset of illnessOpticsPatientsPlasmidsProductionProteinsPublicationsRNAReagentRecording of previous eventsRecoveryRegenerative MedicineResearchResearch PersonnelResource DevelopmentResourcesRoleScienceScientistSequence HomologsSeriesSiteSite VisitSystemTechniquesTechnologyTestingTrainingUniversitiesWorkZebrafishactivation-induced cytidine deaminasebody systemcostdesignempowermentexperimental studygene functiongene productgene replacementgene therapygenetic manipulationhuman diseasehuman modelimprovedinduced pluripotent stem cellinterestmembermethod developmentmodel organismmutantnucleaseprogramsrecombinaserepairedrestorationsite-specific integrationtherapeutic developmenttooltool developmenttranscription activator-like effector nucleasestransmission processvectorzebrafish developmentzebrafish genome
项目摘要
The goals of this application are to apply tools and refine methodologies for
genome engineering in zebrafish that allow the creation of mutagenic and conditional
alleles that provide spatial and temporal control of gene expression. In doing so we will be able
to define genes that aid in the development and implementation of methodology to improve our
understanding of genetic manipulations that can promote or restore health. The ability to make
site-specific, untagged mutant alleles in zebrafish and other models has been greatly advanced
by custom nucleases that include TALENs and CRISPR/Cas9 systems. These systems operate
on the same principle: they are designed to bind to specific sequences in the genome and
create a double strand break. During the first granting cycle, we have leveraged this ability to
develop reliable methods for site-specific gene integration directed by short regions of
homologous sequence. In our renewal application, we utilize the tools, vectors and
methodologies generated to create both revertible alleles and Cre/Cre-ER lines for the zebrafish
community in Aim 1. In Aim 2, we will examine methodologies to improve site-specific
integration and the role of microhomology at CRISPR/Cas9 cut sites and new ways to present
the vector with microhomology to the genomic cut site. In Aim 3, we will continue to develop and
implement targeted integration resources by hosting workshops and onsite visits at both the
Mayo Clinic and Iowa State University. The tools, techniques and zebrafish lines produced will
have direct implications for providing precise gene editing techniques and critical lines to
examine genes with the potential to restore human health. We anticipate these methodologies
will enhance the efficiency of gene editing and will be readily adaptable for use in other model
organisms and large animals. In our opinion, this will have important implications for modeling
human disease in animal systems through the ability to utilize conditional alleles. The methods,
cargos and zebrafish lines are designed to significantly enhance identification of genes that
promote health through leveraging genome modification to produce conditional and revertible
alleles and alleles that mirror mutations in humans.
这个应用程序的目标是应用工具和改进方法
项目成果
期刊论文数量(0)
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专利数量(0)
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KARL J CLARK的其他文献
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{{ truncateString('KARL J CLARK', 18)}}的其他基金
Development of tools for site-directed analysis of gene function
基因功能定点分析工具的开发
- 批准号:
10187374 - 财政年份:2020
- 资助金额:
$ 76.81万 - 项目类别:
Development and genetics of rapid neuroendocrine stress response
快速神经内分泌应激反应的发育和遗传学
- 批准号:
9796476 - 财政年份:2019
- 资助金额:
$ 76.81万 - 项目类别:
Development and genetics of rapid neuroendocrine stress response
快速神经内分泌应激反应的发育和遗传学
- 批准号:
10397544 - 财政年份:2019
- 资助金额:
$ 76.81万 - 项目类别:
Development and genetics of rapid neuroendocrine stress response
快速神经内分泌应激反应的发育和遗传学
- 批准号:
10292709 - 财政年份:2019
- 资助金额:
$ 76.81万 - 项目类别:
Development and genetics of rapid neuroendocrine stress response
快速神经内分泌应激反应的发育和遗传学
- 批准号:
10389006 - 财政年份:2019
- 资助金额:
$ 76.81万 - 项目类别:
Development and genetics of rapid neuroendocrine stress response
快速神经内分泌应激反应的发育和遗传学
- 批准号:
10601205 - 财政年份:2019
- 资助金额:
$ 76.81万 - 项目类别:
Building the mitochondrial genome editing repertoire
构建线粒体基因组编辑库
- 批准号:
10447041 - 财政年份:2018
- 资助金额:
$ 76.81万 - 项目类别:
Building the mitochondrial genome editing repertoire
构建线粒体基因组编辑库
- 批准号:
10220697 - 财政年份:2018
- 资助金额:
$ 76.81万 - 项目类别:
Building the mitochondrial genome editing repertoire
构建线粒体基因组编辑库
- 批准号:
9767023 - 财政年份:2018
- 资助金额:
$ 76.81万 - 项目类别:
Development of tools for site-directed analysis of gene function
基因功能定点分析工具的开发
- 批准号:
10185650 - 财政年份:2016
- 资助金额:
$ 76.81万 - 项目类别:
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