Ed therapeutic interventions. Procedures: We've developed a set of synthetic-biology-inspired genetic SIRT1 list devices that

Ed therapeutic interventions. Procedures: We’ve developed a set of synthetic-biology-inspired genetic SIRT1 list devices that allow effective customizable in situ-production of designer exosomes in engineered mammalian cells, and pursued their therapeutic applications. Outcomes: The created synthetic devices that can be genetically encoded in exosome producer cells (named “EXOtic (EXOsomal Transfer Into Cells) devices”) enhance exosome production, PAK6 manufacturer particular mRNA packaging and delivery of your 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 efficient cell-to-cell communication with no the need to concentrate exosomes. Further, the engineered exosome producer cells implanted in living mice could consistently provide mRNA for the brain. Furthermore, therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in each an in vitro and in vivo Parkinson’s disease model. Summary/Conclusion: These benefits indicate the possible usefulness of the EXOtic devices for RNA delivery-based therapeutic applications. (Nat. Commun. 2018, 9, 1305) Funding: This function was supported by the European Research Council (ERC) advanced grant [ProNet, no. 321381] and in element 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 System.OT06.Engineering designer exosomes produced efficiently by mammalian cells in situ and their application for the therapy of Parkinson’s disease Ryosuke Kojimaa, Daniel Bojarb and Martin Fusseneggerc Graduate College 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 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 data transmitters in a variety of biological contexts, and are candidate therapeutic agents as a new class of drug delivery vesicles. Nevertheless,Introduction: To date a variety of reports have shown the utility of extracellular vesicles (EVs) for delivery of therapeutic protein cargo. At the moment, one of the most typical strategies for loading therapeutic cargoes occur 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 alternative approach is usually to modify releasing cells to secrete EVs containing the desired cargo with minimal impact on native EVs by postisolation remedies. In this study, we designed different constructs to evaluate Cre and Cas9 loading efficiency into EVs using (1) light-induced dimerization systems (Cryptochrome two (CRY2), Phytochrome B.