title: Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes.
abstract: Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in cancer therapy, several technical obstacles must first be overcome. The major hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell's plasma membrane. This study demonstrates that exosome vesicles derived from humans can deliver short interfering RNA (siRNA) to human mononuclear blood cells. Exosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication, i.e. antigen presentation, tolerance development and shuttle RNA (mainly mRNA and microRNA). Having tested different strategies, an optimized method (electroporation) was used to introduce siRNA into human exosomes of various origins. Plasma exosomes (exosomes from peripheral blood) were used as gene delivery vector (GDV) to transport exogenous siRNA to human blood cells. The vesicles effectively delivered the administered siRNA into monocytes and lymphocytes, causing selective gene silencing of mitogen-activated protein kinase 1. These data suggest that human exosomes can be used as a GDV to provide cells with heterologous nucleic acids such as therapeutic siRNAs.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Box 480 and Department of Chemistry and Molecular Biology, Lundberg Laboratory, University of Gothenburg, Box 462, 405 30 Gothenburg, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wahlgren
authors.forename: Tanya
authors.initials: T
authors.lastname: De L Karlson
authors.forename: Mikael
authors.initials: M
authors.lastname: Brisslert
authors.forename: Forugh
authors.initials: F
authors.lastname: Vaziri Sani
authors.forename: Esbjörn
authors.initials: E
authors.lastname: Telemo
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Hadi
authors.initials: H
authors.lastname: Valadi
mesh_terms: D045744:Cell Line, Tumor; D018274:Electroporation; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering