Ed therapeutic interventions. Methods: We’ve got created a set of synthetic-biology-inspired genetic devices that allow efficient customizable in situ-production of designer exosomes in engineered mammalian cells, and pursued their therapeutic applications. Final results: The created synthetic devices that may be genetically encoded in exosome producer cells (named “EXOtic (EXOsomal Transfer Into Cells) devices”) boost exosome production, precise mRNA packaging and delivery with the mRNA into the cytosol of recipient cells. Synergistic use of those devices having a targeting moiety significantly enhanced functional mRNA delivery into recipient cells, enabling effective cell-to-cell communication without the need of the require to concentrate exosomes. Additional, the engineered exosome producer cells implanted in living mice could regularly deliver mRNA towards the brain. Additionally, therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in both an in vitro and in vivo Parkinson’s illness model. Summary/Conclusion: These final results indicate the potential usefulness in the EXOtic devices for RNA delivery-based therapeutic applications. (Nat. Commun. 2018, 9, 1305) Funding: This function was supported by the European Investigation Council (ERC) sophisticated grant [ProNet, no. 321381] and in aspect by the National Centre of Competence in Analysis (NCCR) for Molecular Systems Engineering (to M.F.). R.K. was supported by a postdoctoral fellowship in the Human Frontier Science Program.OT06.Engineering designer exosomes developed effectively by mammalian cells in situ and their application for the therapy of Parkinson’s illness Ryosuke Kojimaa, Daniel Bojarb and Martin Fusseneggerc Graduate School of Medicine, The University of Tokyo. JST PRESTO, Tokyo, Japan; bETH Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland; cETH Zurich, Division of Biosystems Science and Engineering. University of Basel, Faculty of Science, Basel, SwitzerlandaOT06.Protein engineering for loading of Extracellular Vesicles Xabier Osteikoetxeaa, Josia Steina, Elisa L aro-Ib ezb, Gwen O riscollc, Olga Shatnyevad, Rick CD150 Proteins Species Daviesa and Niek Dekkerca cAstraZeneca, Macclesfield, UK; bAstraZeneca, molndal, AstraZeneca, M ndal, Sweden; dAstraZeneca, Molndal, SwedenSweden;Introduction: Exosomes are cell-derived extracellular nanovesicles 5050 nm in size, which serve as intercellular information transmitters in different biological contexts, and are candidate therapeutic agents as a new class of drug delivery vesicles. Nevertheless,Introduction: To date different reports have shown the utility of extracellular vesicles (EVs) for delivery of therapeutic protein cargo. At the moment, the most widespread methods for loading therapeutic cargoes happen just after EV isolation mixing EVs with preferred cargo and subjecting to passive incubation, electroporation, freeze-thaw cycling, sonication, extrusion, or membrane permeabilization with saponin among variousISEV2019 ABSTRACT BOOK AstraZeneca, M ndal, Sweden; bAstraZeneca, molndal, AstraZeneca, Molndal, Sweden; dAstraZeneca, Vancouver, e AstraZeneca, Manchester, United Kingdomc atechniques. An alternative approach is always to modify releasing cells to secrete EVs containing the preferred cargo with minimal effect on native EVs by postisolation remedies. In this study, we developed various constructs to compare Cre and Cas9 loading efficiency into EVs making use of (1) light-induced dimerization systems (CD11c/Integrin alpha X Proteins MedChemExpress Cryptochrome two (CRY2), Phytochrome B.