Ed therapeutic interventions. Techniques: We’ve got developed 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 created synthetic devices that can be genetically encoded in exosome producer cells (named “EXOtic (EXOsomal Transfer Into Cells) devices”) boost exosome production, specific mRNA packaging and delivery of the mRNA in to the cytosol of recipient cells. Synergistic use of these devices having a targeting moiety drastically enhanced functional mRNA delivery into recipient cells, enabling efficient cell-to-cell communication without having the will need to concentrate exosomes. Additional, the engineered exosome producer cells implanted in living mice could consistently provide mRNA to the brain. Moreover, therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in each an in vitro and in vivo Parkinson’s illness model. Summary/Conclusion: These results indicate the possible usefulness of your EXOtic devices for RNA delivery-based therapeutic applications. (Nat. Commun. 2018, 9, 1305) Funding: This perform was supported by the European Research Council (ERC) advanced grant [ProNet, no. 321381] and in aspect by the National Centre of Competence in Study (NCCR) for Molecular Systems Engineering (to M.F.). R.K. was supported by a postdoctoral fellowship in the Human Frontier Science Plan.OT06.Engineering designer exosomes developed efficiently by mammalian cells in situ and their application for the therapy of Parkinson’s illness Ryosuke Kojimaa, Daniel Bojarb and Martin Fusseneggerc Graduate College of Medicine, The University of Tokyo. JST PRESTO, Tokyo, Japan; bETH Zurich, Division 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 Oxytocin Proteins Species Extracellular Fc Receptor-like 4 Proteins medchemexpress 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, Sweden; dAstraZeneca, Molndal, SwedenSweden;Introduction: Exosomes are cell-derived extracellular nanovesicles 5050 nm in size, which serve as intercellular information and facts transmitters in various biological contexts, and are candidate therapeutic agents as a new class of drug delivery vesicles. On the other hand,Introduction: To date several reports have shown the utility of extracellular vesicles (EVs) for delivery of therapeutic protein cargo. At the moment, the most frequent methods for loading therapeutic cargoes take place 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 amongst variousISEV2019 ABSTRACT BOOK AstraZeneca, M ndal, Sweden; bAstraZeneca, molndal, AstraZeneca, Molndal, Sweden; dAstraZeneca, Vancouver, e AstraZeneca, Manchester, United Kingdomc atechniques. An alternative approach is to modify releasing cells to secrete EVs containing the preferred cargo with minimal influence on native EVs by postisolation treatment options. Within this study, we created distinct constructs to evaluate Cre and Cas9 loading efficiency into EVs employing (1) light-induced dimerization systems (Cryptochrome two (CRY2), Phytochrome B.