A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
基本信息
- 批准号:10624895
- 负责人:
- 金额:$ 112.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAllelesAnimalsAreaAssisted Reproductive TechnologyBiologyBiopsy SpecimenBrainBrain DiseasesBreedingCallithrixCallithrix jacchus jacchusCell modelChromosomesClustered Regularly Interspaced Short Palindromic RepeatsCryopreservationDepositionDevelopmentDiagnosticDisease modelEmbryoEmbryo TransferEngineeringEnhancersEssential GenesEvaluationFemaleFrequenciesFunctional disorderGene FrequencyGenerationsGeneticGenetic EngineeringGenetic ModelsGenomeGenome engineeringGenotypeGoalsHeterozygoteHumanInjectionsKnock-inMacacaMethodsMethyl-CpG-Binding Protein 2ModelingModernizationMolecularMosaicismMusNeurosciencesNeurosciences ResearchOocytesPersonsPreimplantation DiagnosisPrimatesProcessProtocols documentationReagentReproductive TechniquesResearchResource SharingRett SyndromeRodentRodent ModelSexual MaturationSingle Nucleotide PolymorphismStandardizationStructureStudy modelsSynaptic plasticitySystemTechnologyTestingTimeTrainingTransposaseUnited States National Institutes of HealthWorkassisted reproductionautism spectrum disorderbase editingbase editorcostdata hubembryo culturegenetic manipulationgenetic testinggenome editingimprovedin vivoinfancymodel organismmutantnonhuman primatenoveloocyte maturationprenatalprime editingprogramsrepairedtooltraittranslational neurosciencezygote
项目摘要
PROJECT SUMMARY
While mice are essential models for many areas of neuroscience, there are also many aspects of
higher brain function and dysfunction that cannot be adequately modeled in rodents. Thus, there is a need for
new genetic models that have brain structure and function closer to humans. For these reasons, non-human
primates (NHP) provide an attractive model to study higher brain function and brain disorders. A promising
emerging NHP model is the common marmoset, a small New World primate that has many advantages as a
genetic model. Although the adaptation of bacterial CRISPR/Cas systems for targeted genome engineering
and model creation has revolutionized modern biology, editing of the marmoset genome is still in its infancy.
Given the significant time and money required for marmoset genome editing, new methods to increase editing
efficiency, decrease mosaicism, and identify correctly-edited embryos prior to transfer to recipient females are
critical. Additionally, new methods for controlling the zygosity of founder animals are necessary to enable
analysis of homozygous F0 animals and to avoid homozygous editing when targeting essential genes that
cause embryonic lethality upon biallelic disruption. To these ends, we propose a research program that will
significantly enhance our ability to introduce multiple types of edits into the marmoset genome, reduce
mosaicism, control the zygosity of edits, and identify successfully edited embryos through prenatal genetic
testing. We will disseminate these technologies and models through direct resource sharing, in-person
trainings, deposition to NIH-supported Marmoset Coordination Center. Together, the proposed advances will
significantly reduce the time, effort, costs and animal numbers necessary to marmoset genetic models and will
unlock the true potential of marmosets for basic and translational neuroscience research.
项目总结
虽然小鼠是神经科学许多领域的基本模型,但也有许多方面
更高的大脑功能和功能障碍,不能在啮齿类动物身上充分建模。因此,有必要
大脑结构和功能更接近人类的新遗传模型。出于这些原因,非人类
灵长类动物(NHP)为研究高级脑功能和脑疾病提供了一个有吸引力的模型。一个有希望的人
新兴的NHP模式是常见的绒猴,一种小型的新大陆灵长类动物,作为一种
遗传模型。尽管细菌CRISPR/Cas系统对靶向基因组工程的适应性
而模型的创建已经给现代生物学带来了革命性的变化,对绒猴基因组的编辑仍处于起步阶段。
考虑到绒猴基因组编辑所需的大量时间和金钱,增加编辑的新方法
效率,减少嵌合体,并在移植给受体雌性之前识别正确编辑的胚胎是
危急时刻。此外,控制创始动物合子的新方法是必要的,以使
对纯合的F0动物进行分析,并在针对以下必需基因时避免纯合编辑
在双等位基因破坏时导致胚胎死亡。为此,我们提出了一个研究计划,该计划将
显著增强我们在绒猴基因组中引入多种类型编辑的能力,减少
嵌合体,控制编辑的合并度,通过产前遗传鉴定成功编辑的胚胎
测试。我们将通过面对面的直接资源共享来传播这些技术和模式
培训,向NIH支持的Marmoset协调中心交纳。加在一起,拟议的进展将
显著减少构建基因模型和意愿所需的时间、精力、成本和动物数量
释放绒猴在基础和翻译神经科学研究中的真正潜力。
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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Guoping Feng其他文献
Guoping Feng的其他文献
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{{ truncateString('Guoping Feng', 18)}}的其他基金
BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution
大脑连接:具有单轴突和细胞类型分辨率的狨猴综合区域投影图
- 批准号:
10664170 - 财政年份:2023
- 资助金额:
$ 112.04万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10622039 - 财政年份:2022
- 资助金额:
$ 112.04万 - 项目类别:
Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
- 批准号:
10653998 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10286437 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10459550 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
- 批准号:
10478105 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
A Genetic Engineering Toolbox for Marmosets (GETMarm): Development and optimization of genome editing and assisted reproduction techniques for marmoset models
狨猴基因工程工具箱 (GETMarm):狨猴模型基因组编辑和辅助生殖技术的开发和优化
- 批准号:
10832288 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
Developing cell type-specific enhancers and connectivity mapping pipelines for marmosets
开发狨猴的细胞类型特异性增强剂和连接映射管道
- 批准号:
10271630 - 财政年份:2021
- 资助金额:
$ 112.04万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10408808 - 财政年份:2019
- 资助金额:
$ 112.04万 - 项目类别:
Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks
通过基因定义的 TRN 子网络对丘脑皮质相互作用进行功能剖析
- 批准号:
10198061 - 财政年份:2019
- 资助金额:
$ 112.04万 - 项目类别:
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