AnteroTag, a Novel Method for Trans-Synaptic Delivery of Active Agents to Map and Modify Anterograde Populations
AnteroTag,一种跨突触传递活性剂以绘制和修改顺行群体的新方法
基本信息
- 批准号:10258693
- 负责人:
- 金额:$ 230.48万
- 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:2021-09-13 至 2024-09-12
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAllelesAmino Acid SequenceAnimal ModelAnimalsApoptosisAreaAxonBRAIN initiativeBehavior ControlBenchmarkingBiologicalBiological AssayBiological ProductsBiologyBrainBrain DiseasesBrain regionCell CountCell NucleusCellsCessation of lifeChronicComplexCre driverDataDependovirusDevelopmentElectrophysiology (science)EngineeringFerretsFunctional ImagingFutureGoalsGrantHerpes Simplex InfectionsHistologyHumanImageInflammationInjectionsLabelMapsMethodsMicroscopyModelingMolecularMolecular TargetMolecular WeightMonitorMusNerve DegenerationNeuronsOrganismOutcomePathway interactionsPerformancePeroxidasesPontine structurePopulationPropertyProtein EngineeringProteinsRabiesReporterResearchResearch PersonnelSafetySerotypingSliceSpecificitySynapsesSynaptic VesiclesSystemTarget PopulationsTechnologyTertiary Protein StructureTestingTherapeuticTherapeutic AgentsTimeTissuesToxic effectTropismTupaiidaeValidationVariantVesicular stomatitis Indiana virusViralViral VectorVirusWheat Germ AgglutininsWorkbasebiomaterial compatibilitycell typecohortcytotoxicdiscrete timegranule cellimprovedin vivoinsightmossy fiberneural circuitneurotransmissionnew technologynonhuman primatenovelnovel therapeuticsnucleasepostsynapticpresynapticprotein transportrecombinasered fluorescent proteinrelating to nervous systemtoolvectorvector controlvesicular release
项目摘要
PROJECT SUMMARY
A goal of the BRAIN initiative is to develop and validate novel tools to map and manipulate neural circuits. The
definition and control of behaviorally relevant circuits requires both retrograde and anterograde trans-synaptic
technologies that perform well in vivo. In this project, we pursue the long-term goal of developing a small protein
tag for the anterograde delivery of cargos (an “AnteroTag”). The novel concept of AnteroTag is to leverage the
endogenous biology of neurotransmission to target tagged payloads to synaptic vesicles where they undergo
vesicular release, postsynaptic entry, and desired action. Our consortium of investigators proposes to utilize the
pontocerebellar circuit as a model pipeline to further refine and rigorously validate AnteroTag. As the axons of
basal pontine neurons (mossy fibers) make specific and quantitative synapses upon cerebellar granule cells, the
pontocerebellar circuit affords an established and conserved model circuit to determine how iterations of
AnteroTag alter its performance. The investigators of the consortium will leverage their respective areas of
expertise to quantify the specificity and biocompatibility of AnteroTag, benchmarked against a current state-of-
the-art anterograde viral vector HSV-129; these analyses in mice will include microscopy, electrophysiology, and
in vivo activity imaging in behaving animals. Once the pipeline determines the most specific and safe version of
AnteroTag in the pontocerebellar circuit, we will assay AnteroTag performance when delivered to diverse starter
populations of neurons. The broad utility of AnteroTag will then be determined by testing its efficacy to deliver a
variety of genetically encoded markers and modifiers, and by testing AnteroTag derivatives for their utility in
accessing second-order anterograde populations. With safety, specificity, and utility thus rigorously
demonstrated in mice, we will assay the performance of AnteroTag in the pontocerebellar circuit of higher
organisms including tree shrews, ferrets, and NHPs. The outcome of this proposal will be the development,
validation, and implementation of a novel technology for the trans-synaptic anterograde delivery of biological
agents across multiple brain regions and multiple species. Thus, if successful, our project will ultimately aid in
the development of targeted cell-type and circuit-specific therapeutics to treat brain disorders.
项目概要
BRAIN 计划的目标是开发和验证绘制和操纵神经回路的新工具。这
行为相关回路的定义和控制需要逆行和顺行跨突触
在体内表现良好的技术。在这个项目中,我们追求开发一种小蛋白质的长期目标
用于顺行运送货物的标签(“AnteroTag”)。 AnteroTag 的新颖概念是利用
神经传递的内源生物学将标记的有效负载靶向它们经历的突触小泡
囊泡释放、突触后进入和所需的作用。我们的研究人员联盟建议利用
脑桥小脑回路作为模型管道,进一步完善和严格验证 AnteroTag。作为轴突
基底脑桥神经元(苔藓纤维)在小脑颗粒细胞上形成特异性和定量的突触,
脑桥小脑电路提供了一个已建立且保守的模型电路,以确定如何迭代
AnteroTag 改变其性能。该联盟的研究人员将利用各自领域的研究成果
量化 AnteroTag 的特异性和生物相容性的专业知识,以当前状态为基准
最先进的顺行病毒载体HSV-129;这些对小鼠的分析将包括显微镜、电生理学和
行为动物的体内活动成像。一旦管道确定了最具体和最安全的版本
AnteroTag 在脑桥小脑回路中,我们将测试 AnteroTag 在传送到不同启动器时的性能
神经元群体。然后,将通过测试 AnteroTag 的功效来确定其广泛的实用性,以提供
各种基因编码标记和修饰符,并通过测试 AnteroTag 衍生物在
访问二阶顺行人群。具有安全性、特异性和实用性,因此严格
在小鼠中得到证实,我们将检测 AnteroTag 在高等脑桥小脑回路中的性能
生物体,包括树鼩、雪貂和 NHP。该提案的结果将是发展,
验证和实施一种用于跨突触顺行传递生物制剂的新技术
跨多个大脑区域和多个物种的代理。因此,如果成功,我们的项目最终将有助于
开发用于治疗脑部疾病的靶向细胞类型和电路特异性疗法。
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 }}
Jason M Christie其他文献
Jason M Christie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('Jason M Christie', 18)}}的其他基金
Cerebellar pathology in the absence of plasticity gating
缺乏可塑性门控的小脑病理学
- 批准号:
10289334 - 财政年份:2021
- 资助金额:
$ 230.48万 - 项目类别:
Cerebellar pathology in the absence of plasticity gating
缺乏可塑性门控的小脑病理学
- 批准号:
10440493 - 财政年份:2021
- 资助金额:
$ 230.48万 - 项目类别:
Cerebellar pathology in the absence of plasticity gating
缺乏可塑性门控的小脑病理学
- 批准号:
10619581 - 财政年份:2021
- 资助金额:
$ 230.48万 - 项目类别:
Organization of inhibition in the cerebellar cortex
小脑皮质的抑制组织
- 批准号:
10877237 - 财政年份:2020
- 资助金额:
$ 230.48万 - 项目类别:
Organization of inhibition in the cerebellar cortex
小脑皮质的抑制组织
- 批准号:
10349928 - 财政年份:2020
- 资助金额:
$ 230.48万 - 项目类别:
Regulation of instructive signaling in the cerebellum
小脑指导信号的调节
- 批准号:
10237314 - 财政年份:2018
- 资助金额:
$ 230.48万 - 项目类别:
Regulation of instructive signaling in the cerebellum
小脑指导信号的调节
- 批准号:
9977802 - 财政年份:2018
- 资助金额:
$ 230.48万 - 项目类别:
相似海外基金
Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
- 批准号:
502556 - 财政年份:2024
- 资助金额:
$ 230.48万 - 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
- 批准号:
10659303 - 财政年份:2023
- 资助金额:
$ 230.48万 - 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
- 批准号:
10674405 - 财政年份:2023
- 资助金额:
$ 230.48万 - 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
- 批准号:
10758772 - 财政年份:2023
- 资助金额:
$ 230.48万 - 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
- 批准号:
10676499 - 财政年份:2023
- 资助金额:
$ 230.48万 - 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
- 批准号:
2748611 - 财政年份:2022
- 资助金额:
$ 230.48万 - 项目类别:
Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
- 批准号:
10532032 - 财政年份:2022
- 资助金额:
$ 230.48万 - 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
- 批准号:
22K05630 - 财政年份:2022
- 资助金额:
$ 230.48万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
- 批准号:
10525070 - 财政年份:2022
- 资助金额:
$ 230.48万 - 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
- 批准号:
10689017 - 财政年份:2022
- 资助金额:
$ 230.48万 - 项目类别:














{{item.name}}会员




