title: Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse.
abstract: Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Dameng
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Zhengya
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Danping
authors.initials: D
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Xihan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yuda
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Zhanzhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Waner
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Geyu
authors.initials: G
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055354:Exosomes / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D051379:Mice; D009020:Morphine / Q000378:metabolism; D009021:Morphine Dependence / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000627:therapeutic use; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D006023:Glycoproteins; C485764:OPRM1 protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017450:Receptors, Opioid, mu; D014764:Viral Proteins; C583075:rabies virus glycoprotein peptide; D009020:Morphine