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

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：病毒式创新核心 当代关于成瘾的神经科学的研究利用了一系列广泛的基因编码工具， 可用于控制神经元兴奋性，突出形成微电路的神经元之间的连接性，以及 报告行为动物的细胞活性状态，利用腺病毒的有益特征。 相关病毒 (AAV) 主干已被证明对于将基因编码工具传递到特定细胞具有无价的价值 神经系统中的类型和回路，是成瘾神经科学界使用的关键工具 明尼苏达大学（UMN）最近在招聘方面进行了投资，以发展与成瘾相关的研究。 在 UMN，对高质量和高效 AAV 载体生产的需求将在未来大幅增加 病毒创新核心 (VIC) 致力于满足 UMN 成瘾研究的 AAV 载体需求。 社区，为中心研究人员和附属机构提供先进的实验性 AAV 访问权限 生产服务，以及一套严格的质量控制和产品评估流程，这些流程将告知 未来基于 AAV 的调查的优化设计 VIC 的任务概括为两个具体任务。 目标：1) AAV 载体的生成和高级表征 VIC 将支持 AAV 的生成。 UMN 成瘾研究界的载体（包括定制载体）将采用严格的标准。 产品评估和质量控制的过程，总的来说，将代表一个全面的概况 病毒质量可用于帮助优化载体生产和纯化方法。 结合特定应用的反馈，将帮助 VIC 在设计、使用和 通过拥有熟练员工的集中实体提供这种劳动密集型服务。 代表了VIC用户群的关键效率，并将有利于集中审查、评估、 以及对来自大量矢量工具的数据的解释 2) AAV 的工程取向。 还将指导一项研究和开发（特别项目）计划，目标是开发新的 围绕 UMN 成瘾的特定需求，改进 AAV 载体递送的方法 VIC 将调查是否用抗体或其他物质“武装”向性无效的 AAV 载体。 非免疫球蛋白支架可以以用户指定的方式重新定义其向性。 将使病毒基因传递基于一个或多个表面受体或标记，将代表一种强大的 实现与成瘾相关的神经回路的精确操作的方法总结/影响。 VIC 生成的数据将促进结构电路核心和成像单元的参与 行为核心，促进将在成瘾连接组核心中整合的见解。 VIC 还将产生协同效应，扩大支持项目的范围并提高 UMN 的影响力 此外，新的多模式 AAV 靶向范式将代表一种新的方法。 为更广泛的内部和外部神经科学研究界带来巨大利益。