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

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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.