title: A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA.
abstract: Recent advances in efficient microRNA (miRNA) delivery techniques using brain-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated neurological diseases. Here, we report the rabies virus glycoprotein (RVG)-labeled non-toxic SSPEI nanomaterials capable of neuron-specific miR-124a delivery to neuron in vivo. The RVG-labeled BPEI-SS (RVG-SSPEI) nanocarrier showed less toxicity in acetylcholine receptor-positive Neuro2a cells, and electrostatic interaction of RVG-SSPEI with miR-124a exhibited optimal transfection efficacy. The RVG-SSPEI polymer specifically targeted Neuro2a using cy5.5-miR-124a mixed with RVG-SSPEI. The functional action of miR-124a oligomers released from polyplexes in the cytoplasmic region was evaluated by a reporter vector containing a miR-124a -binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. Cy5.5-miR-124a/RVG-SSPEI- injected into mice via tail veins displayed the enhanced accumulation of miR-124a in the isolated brain. Hindrance of the efficient penetration of neuronal cells by size limitation of the miR-124a/RVG-SSPEI improved with the help of mannitol through blood-brain barrier disruption. These findings indicated that the RVG peptide combined with mannitol infusion using SSPEI polymer for neuron-specific targeting in vivo is sufficient to deliver neurogenic microRNA into the brain.
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Seoul National University Hospital, 28 Yongon-Dong, Jongno-Gu, Seoul 110-744, Republic of Korea.
authors.forename: Do Won
authors.initials: DW
authors.lastname: Hwang
authors.forename: Sejin
authors.initials: S
authors.lastname: Son
authors.forename: Jaeho
authors.initials: J
authors.lastname: Jang
authors.forename: Hyewon
authors.initials: H
authors.lastname: Youn
authors.forename: Song
authors.initials: S
authors.lastname: Lee
authors.forename: Duhwan
authors.initials: D
authors.lastname: Lee
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000378:metabolism; D011095:Polyethylenes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011820:Rabies virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004220:Disulfides; D004337:Drug Carriers; D006023:Glycoproteins; D007097:Imines; D035683:MicroRNAs; D011095:Polyethylenes; D011108:Polymers; D014764:Viral Proteins; C505405:poly(ethylene imine)