Ed therapeutic interventions. Methods: We have created a set of synthetic-biology-inspired genetic devices that enable efficient customizable in situ-production of designer exosomes in engineered mammalian cells, and pursued their therapeutic applications. Final results: The developed synthetic devices that may be genetically encoded in exosome producer cells (named “EXOtic (EXOsomal Transfer Into Cells) devices”) enhance exosome production, specific mRNA packaging and delivery in the mRNA into the cytosol of recipient cells. Synergistic use of those devices with a targeting moiety drastically enhanced functional mRNA delivery into recipient cells, enabling efficient cell-to-cell communication with no the require to concentrate exosomes. Further, the engineered exosome producer cells implanted in living mice could regularly provide mRNA for the brain. Furthermore, therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in both an in vitro and in vivo Parkinson’s disease model. Summary/Conclusion: These results indicate the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications. (Nat. Commun. 2018, 9, 1305) Funding: This operate was supported by the European Research Council (ERC) sophisticated grant [ProNet, no. 321381] and in part by the National Centre of Competence in Investigation (NCCR) for Molecular Systems Engineering (to M.F.). R.K. was supported by a postdoctoral fellowship from the Human Frontier Science Program.OT06.Engineering designer exosomes created efficiently 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, Division of Muscle-Specific Kinase (MuSK) Proteins Gene ID Biosystems Science and Engineering, Basel, Switzerland; cETH Zurich, Department 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 Daviesa and Niek Dekkerca cAstraZeneca, Macclesfield, UK; bAstraZeneca, molndal, AstraZeneca, M ndal, GPR37 Proteins Gene ID Sweden; dAstraZeneca, Molndal, SwedenSweden;Introduction: Exosomes are cell-derived extracellular nanovesicles 5050 nm in size, which serve as intercellular details transmitters in various biological contexts, and are candidate therapeutic agents as a brand new class of drug delivery vesicles. Nevertheless,Introduction: To date various reports have shown the utility of extracellular vesicles (EVs) for delivery of therapeutic protein cargo. Presently, one of the most typical methods for loading therapeutic cargoes occur immediately after EV isolation mixing EVs with desired cargo and subjecting to passive incubation, electroporation, freeze-thaw cycling, sonication, extrusion, or membrane permeabilization with saponin amongst variousISEV2019 ABSTRACT BOOK AstraZeneca, M ndal, Sweden; bAstraZeneca, molndal, AstraZeneca, Molndal, Sweden; dAstraZeneca, Vancouver, e AstraZeneca, Manchester, United Kingdomc atechniques. An option approach should be to modify releasing cells to secrete EVs containing the desired cargo with minimal effect on native EVs by postisolation treatments. Within this study, we developed various constructs to compare Cre and Cas9 loading efficiency into EVs making use of (1) light-induced dimerization systems (Cryptochrome 2 (CRY2), Phytochrome B.