V University, Tel Aviv, Israel; 3Imperial College London, London, UK; 4Cardiovascular Analysis Center, Icahn School of ENPP-2 Proteins supplier Medicine at Mount Sinai, New York, USA; 5Duke-NUS Medical School, 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 strategy to treat Cystic CXCR1 Proteins Biological Activity fibrosis Inna Uliyakina1, Justin Hean1, Andreas Koschinski1, Miguel Lobo1, Samir El Andaloussi1, Alison Mahoney2, Ray Jupp2 and Matthew J. WoodUniversity of Oxford, Oxford, United kingdom; 2UCB Pharma; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomIntroduction: Cystic fibrosis (CF), probably the most widespread life-shortening genetic disorder amongst Caucasians, impacts over 70,000 individuals worldwide. CF is brought on by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, an anion (chloride/bicarbonate)Ischemic illnesses are the top cause of illness and death around the globe. Localised therapeutic angiogenesis capable to enhance the microvascular network could assist the suffering patients by providing additional blood flow to inadequately perfused areas. Exosomes with variable microRNA cargos are released from distinctive progenitor cell sorts and stimulate angiogenesis in animal models. We not too long ago showed that human pericardial fluid (PF) surrounding the heart also consists of exosomes capable to market angiogenesis via the delivery of the microRNA let-7b-5p to recipient hypoxic endothelial cells (ECs). Here, we aimed to: (1) characterise the popular microRNA cargo of endogenous angiogenic exosomes making use of bioinformatics, (2) exploit this expertise to develop off-the-shelf artificial exosomes (AEs) with superior proangiogenic capacities, (3) validate the angiogenic potential in the bioinspired AEs. Pilot bioinformatics analyses integrating data 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 created AEs containing either let-7b-5p or fluorescent cy5-cel-miR-39, as manage. The AEs were uptaken by human ECs and pericytes cultured under hypoxic situations, with no causing toxicity. let-7b-AEs transferred functional let7b, thus decreased the expression of TGFBR1 and CASP3 (validated targets ofScientific Plan 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 muscles resulted in their uptake by 12 and 11 with the local microvascular ECs and pericytes, respectively. All round, our preliminary benefits suggest the therapeutic potential of bioinspired AEs containing let-7b, which will be further developed by: (1) employing clustering methods 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 Wellness, NY, USA; 2National Institute of Biomedical Imaging and Bioengineering, National Institutes of Overall health, NY, USA; 3National Cancer Institute, Vaccine Branch, MD, USAmacrophages to engulf tumour cells, which acts as a significant phagocytic barri.
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