FMRG: Bio: Enabling Technologies for Biomanufacturing Extracellular Vesicle-Based Therapeutics

细胞外囊泡（EV）是被膜包围的流体囊。 细胞创造这些细胞来与其他细胞交换物质和信息。使用EV作为药物载体是可能的。通过修饰囊泡表面的分子，它们可以靶向特定的细胞或细胞类型。大规模生产具有可调和明确特性的纯化电动汽车的技术正在开发中。 这项未来生物制造研究的长期目标是开发设计电动汽车的可扩展制造。该项目将招募一批不同的本科生和高中生。他们将参与指导研究和教学模块的开发，向纳什维尔公立学校区的本科生和学生介绍数字制造和基于细胞的制造概念。总体目标是利用控制EV的生产，含量和细胞摄取的细胞过程。核心假设是，组织特异性生产细胞的3D培养和生物分子工程的组合将使治疗性EV的产物产量最大化。EV将被工程化用于RNA的有效装载和细胞内递送。将开发一种可扩展的工作流程，用于从分化的人类诱导多能干细胞（iPSC）生产EV。将扩大从贴壁细胞生产EV的生物制造平台。通过解决突出的知识和技术差距，该研究有望开创新的策略，用于可扩展制造具有广泛临床应用潜力的设计师，组织特异性EV。此外，这项工作将为控制EV生物合成、RNA装载、分泌、细胞摄取和递送的细胞表型提供基本见解。该未来制造奖由ENG的化学、生物工程、环境和运输系统（CBET）部门，ENG的土木、机械和制造创新（CMMI）部门，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Extracellular vesicles (EVs) are sacs of fluid surrounded by a membrane. Cells create these to exchange material and information with other cells. Using EVs to act as drug carriers is possible. By modifying the molecules on the vesicle surface, they can be targeted to specific cells or cell types. The technology to mass-produce purified EVs with tunable and well-defined properties is developing. The long-term goal of this Future BioManufacturing research is to develop scalable manufacturing of designer EVs. A diverse cohort of undergraduate and high school students will be recruited to the project. They will participate in mentored research and the development of instructional modules that introduce digital fabrication and cell-based manufacturing concepts to undergraduates and students in the Metro Nashville Public Schools district. The overall objective is to harness cellular processes that control the production, content, and cellular uptake of EVs. The central hypothesis is that the combination of 3D culture of tissue-specific producer cells and biomolecular engineering will maximize the product yield of therapeutic EVs. EVs will be engineered for efficient loading and intracellular delivery of RNA. A scalable workflow will be developed for producing EVs from differentiated human induced pluripotent stem cells (iPSCs). A biomanufacturing platform that produces EVs from adherent cells will be scaled-up. By addressing outstanding knowledge and technology gaps, the research is expected to pioneer new strategies for scalable manufacturing of designer, tissue specific EVs that have broad potential for clinical applications. In addition, this work will provide fundamental insights into the cellular phenotypes that control EV biosynthesis, RNA loading, secretion, cellular uptake, and delivery.This Future Manufacturing award was supported by the Chemical, Bioengineering, Environmental, and Transport Systems (CBET) Division in ENG, the Civil, Mechanical, and Manufacturing Innovation (CMMI) Division in ENG, and the Molecular and Cellular Biosciences (MCB) Division in BIO.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.