Viral Innovation Core

病毒式创新核心

• 批准号: 10634615
• 负责人: KEVIN D WICKMAN
• 金额: $ 42.67万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634615
• 关键词: Animals; Antibodies; Area; Behavior; Capsid; Cells; Communities; Coupled; Custom; DNA; Data; Data Analyses; Dependovirus; Ectopic Expression; Elements; Encapsulated; Engineering; Enterobacteria phage P1 Cre recombinase; Evaluation; FLP recombinase; Feedback; Future; Gene Delivery; Generations; Genome; Goals; Investigation; Investments; Life; Maps; Measures; Mediating; Medical; Methodology; Minnesota; Mission; Modeling; Mus; Nervous System; Neurons; Neurosciences; Neurosciences Research; Nucleic Acid Regulatory Sequences; Performance; Population; Process; Production; Property; Proteins; Quality Control; Rattus; Reporting; Research; Research Personnel; Research Project Grants; Risk; Serotyping; Services; Specific qualifier value; Specificity; Surface; Tertiary Protein Structure; Tissues; Transgenes; Transgenic Animals; Transgenic Organisms; Tropism; Universities; Vertebral column; Viral; Viral Vector; Virus; addiction; adeno-associated viral vector; arm; base; cell type; cellular imaging; connectome; data acquisition; design; improved; innovation; insight; interest; multimodality; neural circuit; neuronal excitability; nonhuman primate; permissiveness; programs; promoter; receptor; recombinase; research and development; scaffold; screening; skills; success; synergism; tool; transduction efficiency; vector; viral gene delivery; virus tropism; Animals; Antibodies; Area; Behavior; Capsid; Cells; Communities; Coupled; Custom; DNA; Data; Data Analyses; Dependovirus; Ectopic Expression; Elements; Encapsulated; Engineering; Enterobacteria phage P1 Cre recombinase; Evaluation; FLP recombinase; Feedback; Future; Gene Delivery; Generations; Genome; Goals; Investigation; Investments; Life; Maps; Measures; Mediating; Medical; Methodology; Minnesota; Mission; Modeling; Mus; Nervous System; Neurons; Neurosciences; Neurosciences Research; Nucleic Acid Regulatory Sequences; Performance; Population; Process; Production; Property; Proteins; Quality Control; Rattus; Reporting; Research; Research Personnel; Research Project Grants; Risk; Serotyping; Services; Specific qualifier value; Specificity; Surface; Tertiary Protein Structure; Tissues; Transgenes; Transgenic Animals; Transgenic Organisms; Tropism; Universities; Vertebral column; Viral; Viral Vector; Virus; addiction; adeno-associated viral vector; arm; base; cell type; cellular imaging; connectome; data acquisition; design; improved; innovation; insight; interest; multimodality; neural circuit; neuronal excitability; nonhuman primate; permissiveness; programs; promoter; receptor; recombinase; research and development; scaffold; screening; skills; success; synergism; tool; transduction efficiency; vector; viral gene delivery; virus tropism

PROJECT SUMMARY: Viral Innovation Core Contemporary research on the neuroscience of addiction utilizes a broad set of genetically encoded tools that can be used to control neuronal excitability, highlight connectivity between neurons that form microcircuits, and report cellular activity states in behaving animals. Viral vectors exploiting the beneficial features of the Adeno- Associated Virus (AAV) backbone have proven invaluable for delivering genetically encoded tools to specific cell types and circuits in the nervous system, and are critical tools used by the addiction neuroscience community at the University of Minnesota (UMN). With the recent investments made in hiring to grow addiction-related research at UMN, the need for high-quality and efficient AAV vector production will increase substantially over the next decade. The Viral Innovation Core (VIC) seeks to meet the AAV vector needs of the UMN addiction research community, providing Center Investigators and Affiliates with access to advanced and experimental AAV production services, as well as a rigorous set of quality control and product evaluation processes that will inform the optimal design of future AAV-based investigations. The mission of the VIC is encapsulated in two Specific Aims: 1) Generation and advanced characterization of AAV vectors. The VIC will support the generation of AAV vectors – including custom vectors – for the UMN addiction research community. The VIC will employ a stringent process of product evaluation and quality control that, in aggregate, will represent a comprehensive profile of virus quality that can be used to help optimize vector production and purification approaches. This effort, combined with application-specific feedback, will help the VIC best advise investigators on the design, use, and storage of these tools. Providing this labor-intensive service through a centralized entity with skilled staff represents a critical efficiency for the VIC user base, and will facilitate the centralized examination, evaluation, and interpretation of data from a large and broad array of vector tools. 2) Engineering tropism of AAV. The VIC will also direct a research and development (Special Projects) program with the goal of developing new methodologies to improve the delivery of AAV vectors, oriented around the specific needs of the UMN addiction research community. The VIC will investigate whether “arming” tropism-null AAV vectors with antibodies or other non-immunoglobulin scaffolds can redefine their tropism in a user-specified manner. Engineered tropism, which will enable viral gene delivery based on one or more surface receptors or markers, would represent a powerful approach to achieving precise manipulation of neural circuits relevant to addiction. Summary/impact. Tools generated by the VIC will promote engagement with the Structural Circuits Core and Imaging Cells during Behavior Core, fueling insights that will be consolidated within the Addiction Connectome Core. The efforts of the VIC will also yield synergies that expand the scope of supported projects and increase the impact of UMN research in the area of addiction. Furthermore, new multi-modal AAV targeting paradigms will represent a substantial benefit to the broader internal and external neuroscience research communities.

项目摘要：病毒创新核心 关于成瘾神经科学的当代研究利用了一套广泛的遗传编码工具 可用于控制神经元兴奋，突出显示形成微电路的神经元之间的连通性， 报告行为动物中的细胞活性状态。病毒载体利用腺体的有益特征 相关病毒（AAV）主链已证明对将遗传编码工具传递到特定细胞是无价的 神经系统中的类型和电路是成瘾神经科学社区使用的关键工具 明尼苏达大学（UMN）。随着最近在招聘与成瘾有关的研究的投资 在UMN，对高质量和高效的AAV矢量生产的需求将在下一个中大幅增加 十年。病毒创新核心（VIC）试图满足UMN成瘾研究的AAV向量需求 社区，为中心调查人员和分支机构提供了高级和实验性AAV的访问 生产服务以及一套严格的质量控制和产品评估流程，这些过程将告知 未来基于AAV的调查的最佳设计。 VIC的任务封装在两个特定的 目的：1）AAV矢量的产生和高级表征。维克将支持AAV的一代 媒介（包括自定义向量）用于UMN成瘾研究界。维克将雇用严格的雇员 产品评估和质量控制的过程总共代表了 可用于帮助优化媒介生产和纯化方法的病毒质量。这项工作， 结合特定应用程序的反馈，将帮助VIC最好地为调查人员提供有关设计，使用和 这些工具的存储。通过集中式实体提供这项实验室密集型服务 代表VIC用户群的关键效率，并将促进集中式检查，评估， 以及来自大量和广泛的向量工具的数据解释。 2）AAV的工程学归因。维克 还将指导一个研发（特殊项目）计划，以开发新的 改善AAV向量的交付的方法，围绕UMN成瘾的特定需求而定向 研究社区。 VIC将调查“武装” Tropism-null AAV载体是否具有抗体或其他 非免疫球蛋白脚手架可以以用户指定的方式重新定义其对流。工程性的向潮流，这 将基于一个或多个表面受体或标记的病毒基因传递，将代表强大的 实现与成瘾有关的神经回路的精确操纵的方法。摘要/影响。工具 VIC生成的将促进与结构电路核心和成像单元的互动 行为核心，加油将在成瘾连接组核心中巩固的见解。努力 VIC还将产生协同作用，以扩大支持项目的范围并增加UMN的影响 成瘾领域的研究。此外，新的多模式AAV靶向范例将代表 对更广泛的内部和外部神经科学研究社区的重大好处。