title: RNAi delivery by exosome-mimetic nanovesicles - Implications for targeting c-Myc in cancer.
abstract: To develop RNA-based therapeutics, it is crucial to create delivery vectors that transport the RNA molecule into the cell cytoplasm. Naturally released exosomes vesicles (also called "Extracellular Vesicles") have been proposed as possible RNAi carriers, but their yield is relatively small in any cell culture system. We have previously generated exosome-mimetic nanovesicles (NV) by serial extrusions of cells through nano-sized filters, which results in 100-times higher yield of extracellular vesicles. We here test 1) whether NV can be loaded with siRNA exogenously and endogenously, 2) whether the siRNA-loaded NV are taken up by recipient cells, and 3) whether the siRNA can induce functional knock-down responses in recipient cells. A siRNA against GFP was first loaded into NV by electroporation, or a c-Myc shRNA was expressed inside of the cells. The NV were efficiently loaded with siRNA with both techniques, were taken up by recipient cells, which resulted in attenuation of target gene expression. In conclusion, our study suggests that exosome-mimetic nanovesicles can be a platform for RNAi delivery to cell cytoplasm.
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Taral R
authors.initials: TR
authors.lastname: Lunavat
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Su Chul
authors.initials: SC
authors.lastname: Jang
authors.affiliation: Department of Surgery, Sahlgrenska Cancer Center, Institute of Clinical Sciences, University of Gothenburg, Gothenburg 413 90, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nilsson
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hyun Taek
authors.initials: HT
authors.lastname: Park
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Repiska
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lässer
authors.affiliation: Department of Surgery, Sahlgrenska Cancer Center, Institute of Clinical Sciences, University of Gothenburg, Gothenburg 413 90, Sweden.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Nilsson
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: ysgho@postech.ac.kr.
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.affiliation: Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg 405 30, Sweden. Electronic address: jan.lotvall@gu.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000379:methods; D002458:Cell Fractionation / Q000379:methods*; D002460:Cell Line; D018274:Electroporation; D055354:Exosomes / Q000235:genetics*; D005374:Filtration / Q000379:methods; D018014:Gene Transfer Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering
keywords: Drug delivery systems; Exosome-mimetics; Exosomes; Extracellular vesicles; siRNA delivery