V University, Tel Aviv, Israel; 3Imperial College London, London, UK; 4Cardiovascular Research Center, Icahn College

V University, Tel Aviv, Israel; 3Imperial College London, London, UK; 4Cardiovascular Research Center, Icahn College of Medicine at Mount Sinai, New York, USA; 5Duke-NUS Healthcare College, NC, USA; 6Bristol Heart Institute, University of Bristol, Bristol, United KingdomOT1.Exosome-mediated delivery of CFTR protein to human bronchial epithelia as a novel therapeutic tactic to treat Cystic Fibrosis Inna Uliyakina1, Justin Hean1, Andreas Koschinski1, Miguel Lobo1, Samir El Andaloussi1, Alison Mahoney2, Ray Jupp2 and Matthew J. WoodUniversity of Oxford, Oxford, Uk; 2UCB Pharma; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomIntroduction: Cystic fibrosis (CF), one of the most common life-shortening genetic disorder among Caucasians, impacts more than 70,000 individuals Phospholipase Purity & Documentation worldwide. CF is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, an anion (chloride/bicarbonate)Ischemic diseases are the top cause of illness and death about the world. Localised therapeutic angiogenesis capable to enhance the microvascular EGFR Antagonist MedChemExpress network could assistance the suffering patients by supplying extra blood flow to inadequately perfused areas. Exosomes with variable microRNA cargos are released from diverse progenitor cell forms and stimulate angiogenesis in animal models. We not too long ago showed that human pericardial fluid (PF) surrounding the heart also consists of exosomes able to promote angiogenesis through the delivery of the microRNA let-7b-5p to recipient hypoxic endothelial cells (ECs). Here, we aimed to: (1) characterise the frequent microRNA cargo of endogenous angiogenic exosomes working with bioinformatics, (2) exploit this understanding to develop off-the-shelf artificial exosomes (AEs) with superior proangiogenic capacities, (three) validate the angiogenic possible with the bioinspired AEs. Pilot bioinformatics analyses integrating information of miRNA arrays on proangiogenic exosomes (from PF and bone marrow-derived CD34+ cells) confirmed the enrichment of let-7b-5p in these exosomes. Next, we developed AEs containing either let-7b-5p or fluorescent cy5-cel-miR-39, as control. The AEs were uptaken by human ECs and pericytes cultured under hypoxic circumstances, without causing toxicity. let-7b-AEs transferred functional let7b, therefore decreased the expression of TGFBR1 and CASP3 (validated targets ofScientific Program ISEVlet-7b-5p) in recipient cells. let-7b-AEs enhanced EC survival and angiogenesis in vitro. In vivo, cel-miR-39-AEs injection in ischemic murine muscle tissues resulted in their uptake by 12 and 11 of your nearby microvascular ECs and pericytes, respectively. All round, our preliminary final results recommend the therapeutic prospective of bioinspired AEs containing let-7b, which will be further created by: (1) employing clustering tactics to seek out candidate miRNAs grouping with let-7b; (2) functionalising AEs to preferentially target ischemic ECs.OT1.Scalable, cGMP-compatible purification of EV enriched with heterodimeric interleukin-15 Dionysios C. Watson1, Bryant Yung2, Aizea Morales-Kastresana1, Cristina Bergamaschi1, Bhabadeb Chowdhury1, Jennifer C. Jones3, Barbara Felber1, Xiaoyuan Chen2 and George Pavlakis1 National Cancer Institute, National Institutes of Health, NY, USA; 2National Institute of Biomedical Imaging and Bioengineering, National Institutes of Wellness, NY, USA; 3National Cancer Institute, Vaccine Branch, MD, USAmacrophages to engulf tumour cells, which acts as a significant phagocytic barri.