Document text
Principal Investigator: Juliane Nguyen
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2019
Award: $482,859
Funding agency: National Institute of Biomedical Imaging and Bioengineering
PROJECT SUMMARY/ABSTRACT
Exosomes were originally thought of as the cellular “waste-disposal system.” It is now known
that they are important for intercellular communication and contribute to the pathogenesis of
several diseases including cancer, neurodegenerative disease, and autoimmunity. Once
secreted from parental cells, exosomes can be: (a) captured by neighboring cells, and/or (b)
released into the systemic circulation for uptake by distant tissues and organs. Thus, their
effects are not only local but can have far reaching systemic consequences. For example,
cancer invasion and metastasis are promoted by exosomes and their contents.
Currently, no therapeutic strategies exploit pathological crosstalk between cells to interrupt
disease progression; most therapies target intracellular signaling. The goal of this proposal is to
design and synthesize RNA EXO-Codes that are selectively enriched in exosomes. These will
be used to: (i) deliver therapeutic RNAs that will reprogram pathological exosomes in vitro and
in vivo, and (ii) elucidate mechanisms of nucleic acid sorting to exosomes.
Successful completion of this research will result in a platform of zip-code-like biomaterials
capable of selectively loading therapeutic cargo into exosomes. This will lay the foundation for
the development of a novel therapeutic strategy, based on the hijacking of exosomal sorting
machinery, for treating diseases in which exosomes are pathological.
Terms: <Acids><Affinity><Assay><Autoimmune Status><Autoimmunity><Band Shift Mobility Assay><Bandshift Mobility Assay><Behavior><Binding><Binding Proteins><Bio-Informatics><Bioassay><Biocompatible Materials><Bioinformatics><Biologic Assays><Biological><Biological Assay><Biomaterials><Blood Circulation><Bloodstream><Body Tissues><Breast Cancer><Breast Cancer Cell><Breast Cancer Patient><Breast Cancer Prevention><Breast Metastasis><Breast Tumor Patient><Breast cancer metastasis><Cancers><Cell Body><Cell Communication and Signaling><Cell Isolation><Cell Segregation><Cell Separation><Cell Separation Technology><Cell Signaling><Cell to Cell Communication and Signaling><Cell-Cell Signaling><Cells><Circulation><Code><Coding System><Communication><Computer Models><Computer Simulation><Computer based Simulation><Computerized Models><Cytoplasm><Data><Degenerative Neurologic Diseases><Degenerative Neurologic Disorders><Development><Disease><Disease Progression><Disorder><Distant><Docking><Drug Carriers><Drug Delivery><Drug Delivery Systems><Electrophoretic Mobility Shift Assay><Encapsulated><Foundations><G3BP><G3BP1><G3BP1 gene><Gene Transcription><Generations><Genetic Transcription><Genomics><Goals><Heterogeneity><Heterogeneous-Nuclear Ribonucleoprotein L><In Vitro><Individual><Intercept><Interruption><Intracellular Communication and Signaling><Legal patent><Libraries><Ligand Binding Protein><Ligand Binding Protein Gene><Lung><Lung Respiratory System><MDA MB 231><MDA-231><MDA-MB231><Malignant Neoplasms><Malignant Tumor><Mathematical Model Simulation><Mathematical Models and Simulations><Metastasis><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Micro RNA><MicroRNAs><Mobility Shift Assay><Molecular><Molecular Interaction><NGS Method><NGS system><Neoplasm Metastasis><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Non-Polyadenylated RNA><Nucleic Acids><Organ><Patents><Pathogenesis><Pathogenicity><Pathologic><Phenotype><Point Mutation><Process><Protein Binding><Proteins><Proteomics><RNA><RNA Expression><RNA Gene Products><RNA library><Refuse Disposal><Research><Ribonucleic Acid><Role><Secondary Neoplasm><Secondary Tumor><Short interfering RNA><Signal Transduction><Signal Transduction Systems><Signaling><Small Interfering RNA><Sorting - Cell Movement><Surface Plasmon Resonance><System><TNBC><Technology><Testing><Therapeutic><Tissues><Transcription><base><biological material><biological signal transduction><bone><bound protein><breast tumor cell><cancer genetics><cancer metastasis><cell sorting><computational modeling><computational models><computational simulation><computer based models><computerized modeling><computerized simulation><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><design><designing><developmental><exosome><experiment><experimental research><experimental study><gel shift assay><hnRNP L><in silico><in vivo><intercellular communication><lipid nanoparticle><loss of function><malignancy><malignant breast neoplasm><malignant breast tumor><mammary cancer prevention><mammary tumor prevention><miRNA><miRNAs><migration><mouse model><murine model><neoplasm/cancer><neurodegenerative illness><new drug treatments><new drugs><new therapeutics><new therapy><next gen sequencing><next generation sequencing><next generation therapeutics><nextgen sequencing><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><nucleic acid delivery><off-patent><prevent><prevent breast cancer><preventing><protein function><pulmonary><screening><siRNA><social role><sorting><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic RNA><triple-negative breast cancer><triple-negative invasive breast carcinoma><tumor cell metastasis><uptake><virtual simulation><waste disposal>