Viral Innovation Core

项目摘要：病毒式创新核心 当代关于成瘾的神经科学研究利用了一套广泛的遗传编码工具， 可用于控制神经元的兴奋性，突出形成微电路的神经元之间的连接，以及 报告行为动物的细胞活动状态。病毒载体使用腺病毒的有益功能- 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非常宝贵的价值 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，请访问 明尼苏达大学(UMN)。随着最近在招聘方面的投资，以增加与成瘾相关的研究 在UMN，对高质量和高效的AAV媒介生产的需求将在接下来的几年里大幅增加 十年。病毒创新核心(VIC)寻求满足UMN成瘾研究的AAV载体需求 社区，为中心调查人员和附属机构提供访问先进和实验性AAV的途径 生产服务，以及一套严格的质量控制和产品评估流程，将为 未来基于AAV的调查的优化设计。VIC的使命被概括为两个具体的 目的：1)AAV载体的构建及高级特性研究。VIC将支持AAV的生成 UMN成瘾研究社区的载体--包括定制载体。VIC将采用严格的 产品评估和质量控制的过程，总体上将代表 病毒质量，可用于帮助优化载体生产和纯化方法。这一努力， 与特定于应用程序的反馈相结合，将帮助VIC最好地就设计、使用和 这些工具的储存。通过拥有熟练员工的集中式实体提供这项劳动密集型服务 代表VIC用户群的关键效率，并将促进集中检查、评价、 以及从大量和广泛的矢量工具中解释数据。2)AAV的工程化取向。VIC 还将指导一个研究和开发(特殊项目)计划，目标是开发新的 改进AAV媒介交付的方法，以UMN成瘾的特定需求为导向 研究社区。VIC将调查是否用抗体或其他方式“武装”取向为零的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它们的取向。工程取向，这是 将基于一个或多个表面受体或标志物的病毒基因传递，将代表着一种强大的 实现与成瘾相关的神经回路的精确操作的方法。摘要/影响。工具 由VIC生成将促进与结构电路核心和成像细胞的接触 行为核心，激发将在成瘾连接核心中巩固的洞察力。所做的努力 VIC还将产生协同效应，扩大所支持项目的范围，并增加UMN的影响 在成瘾领域的研究。此外，新的多模式AAV目标模式将代表一种 为更广泛的内部和外部神经科学研究界带来实质性的好处。

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.