title: Therapeutic applications of extracellular vesicles: clinical promise and open questions.
abstract: This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury.
authors.affiliation: Molecular Neurogenetics Unit, Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02114.|Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Bence
authors.initials: B
authors.lastname: György
authors.affiliation: Interdepartmental Biological Sciences Graduate Program, Northwestern University, Evanston, Illinois 60208.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Hung
authors.affiliation: Molecular Neurogenetics Unit, Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.affiliation: Department of Chemical and Biological Engineering, Robert H. Lurie Comprehensive Cancer Center, Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois 60208.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Leonard
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles / Q000276:immunology / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D015195:Drug Design; D055354:Exosomes / Q000276:immunology / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles; D036103:Nanotechnology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D012313:RNA / Q000008:administration & dosage* / Q000378:metabolism; D014018:Tissue Distribution; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D014612:Vaccines; D012313:RNA; D004247:DNA
keywords: drug delivery; exosomes; extracellular RNA; gene medicine; gene therapy; liposomes; mesenchymal stem cells; microvesicles; nanoparticles