Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
基本信息
- 批准号:9804329
- 负责人:
- 金额:$ 224.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-22 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsBiological ModelsBloodBlood - brain barrier anatomyBrainCallithrixCapsidCarrying CapacitiesCellsCollaborationsComplexCorpus striatum structureDataDependovirusDevelopmentDiseaseEngineeringEnhancersEnterobacteria phage P1 Cre recombinaseEpilepsyEvolutionExhibitsFunctional disorderGene ExpressionGenesGeneticHumanIndividualInjectionsInstitutesInterneuronsIntravenousMacacaMapsMental disordersMethodsModelingMusNatureNeuronsOrganoidsPerformancePhasePopulationProsencephalonRabiesReagentRecombinant adeno-associated virus (rAAV)RecombinantsRegulator GenesRegulatory ElementSafetySpecificityTarget PopulationsTechnologyTestingTransgenic MiceValidationViralVirusVisual Perceptionadeno-associated viral vectorbasebrain cellbrain circuitrycell typecholinergicexpression vectorhigh throughput screeninghuman diseasehuman modelin vitro Modelin vivoinduced pluripotent stem cellneuroregulationnonhuman primatenoveloptogeneticsscreeningselective expressionsensorsuccesstransgene expressionvector
项目摘要
PROJECT SUMMARY
In this proposal we aim to identify gene regulatory elements that permit the targeting and manipulation of brain
circuit models of human brain function. Gaining genetic access to specific neuron populations in nontransgenic
animals and humans would enable targeted circuit modulation for hypothesis testing and provide a means to
evaluate the safety and efficacy of circuit modulation for the treatment of epilepsy and psychiatric disorders. Our
approach capitalizes on our combined expertise in the development and maturation of brain cell-types and
circuits (Gord Fishell), identification of CIS-regulatory elements that function across species (Jordane
Dimidschstein) and AAV engineering combined with large-scale screening methods (Ben Deverman). Our efforts
will benefit from an ongoing collaboration with John Reynolds at the Salk Institute on observation and
manipulation of cortical circuits during complex visual perception tasks. This project will build upon success that
we and others have had in identifying gene regulatory elements that enable cell type-restricted gene expression
when used within recombinant adeno-associated virus (AAV) vectors. Identifying additional enhancer sequences
that function in the context of the limited carrying capacity of AAV has been slow due to the limited success rate
and low throughput nature of these efforts. Here we aim to apply a novel high-throughput screening approach
for the rapid identification of a suite of enhancers that enable the study and manipulation of genetically defined
cell types and circuits across species. Our preliminary data demonstrates that our enhancer identification
strategy can yield novel and highly specific enhancers that restrict expression to target populations. In addition,
we have demonstrated that it is possible to use the engineered AAV-PHP.eB capsid to screen enhancers across
the brain with a single noninvasive injection. These successes have highlighted the need for more rapid and
comprehensive assessment of putative enhancers. In the UH3 portion of this proposal we will examine the
tolerance to neuronal activity manipulation within the target neuronal populations in several species. We will also
apply the AAV-enhancer viruses for querying disease-related circuits using Rabies tracing in conjunction with
optogenetics. This proposal will be transformative in devising methods to target and manipulate the brain activity
of specific neuronal cell populations across species, including human cell-derived organoids.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Benjamin E Deverman其他文献
Benjamin E Deverman的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Benjamin E Deverman', 18)}}的其他基金
Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia
用于小胶质细胞基因表达的新型 AAV 衣壳和基因调控元件
- 批准号:
10195876 - 财政年份:2021
- 资助金额:
$ 224.87万 - 项目类别:
Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia
用于小胶质细胞基因表达的新型 AAV 衣壳和基因调控元件
- 批准号:
10376863 - 财政年份:2021
- 资助金额:
$ 224.87万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10001022 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10170428 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10612519 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
10455344 - 财政年份:2018
- 资助金额:
$ 224.87万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
10001044 - 财政年份:2018
- 资助金额:
$ 224.87万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
9789390 - 财政年份:2018
- 资助金额:
$ 224.87万 - 项目类别:
Novel AAVs Engineered for Efficient and Noninvasive Cross-Species Gene Editing Throughout the Central Nervous System
专为整个中枢神经系统进行高效、非侵入性跨物种基因编辑而设计的新型 AAV
- 批准号:
10490394 - 财政年份:2018
- 资助金额:
$ 224.87万 - 项目类别:
相似海外基金
Nonlocal Variational Problems from Physical and Biological Models
物理和生物模型的非局部变分问题
- 批准号:
2306962 - 财政年份:2023
- 资助金额:
$ 224.87万 - 项目类别:
Standard Grant
Point-of-care optical spectroscopy platform and novel ratio-metric algorithms for rapid and systematic functional characterization of biological models in vivo
即时光学光谱平台和新颖的比率度量算法,可快速、系统地表征体内生物模型的功能
- 批准号:
10655174 - 财政年份:2023
- 资助金额:
$ 224.87万 - 项目类别:
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
- 批准号:
RGPIN-2015-06573 - 财政年份:2022
- 资助金额:
$ 224.87万 - 项目类别:
Discovery Grants Program - Individual
Micro-electrofluidic platforms for monitoring 3D human biological models
用于监测 3D 人体生物模型的微电流体平台
- 批准号:
DP220102872 - 财政年份:2022
- 资助金额:
$ 224.87万 - 项目类别:
Discovery Projects
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
- 批准号:
RGPIN-2015-06573 - 财政年份:2021
- 资助金额:
$ 224.87万 - 项目类别:
Discovery Grants Program - Individual
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
- 批准号:
RGPIN-2015-06573 - 财政年份:2020
- 资助金额:
$ 224.87万 - 项目类别:
Discovery Grants Program - Individual
Harnessing machine learning and cloud computing to test biological models of the role of white matter in human learning
利用机器学习和云计算来测试白质在人类学习中的作用的生物模型
- 批准号:
2004877 - 财政年份:2020
- 资助金额:
$ 224.87万 - 项目类别:
Fellowship Award
A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models
便携式低成本调查点 CapCell 示波器,用于对体外和体内生物模型中的主要代谢轴和相关脉管系统进行成像和量化
- 批准号:
9899988 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别:
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
- 批准号:
RGPIN-2015-06573 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别:
Discovery Grants Program - Individual
A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models
便携式低成本调查点 CapCell 示波器,用于对体外和体内生物模型中的主要代谢轴和相关脉管系统进行成像和量化
- 批准号:
9753458 - 财政年份:2019
- 资助金额:
$ 224.87万 - 项目类别: