{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:47:38Z","timestamp":1783212458438,"version":"3.54.6"},"reference-count":70,"publisher":"Portico","issue":"1","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuronal axons damaged by traumatic injury are unable to spontaneously regenerate in the mammalian adult central nervous system (CNS), causing permanent motor, sensory, and cognitive deficits. Regenerative failure in the adult CNS results from a complex pathology presenting multiple barriers, both the presence of growth inhibitors in the extrinsic microenvironment and intrinsic deficiencies in neuronal biochemistry, to axonal regeneration and functional recovery. There are many strategies for axonal regeneration after CNS injury including antagonism of growth-inhibitory molecules and their receptors, manipulation of cyclic nucleotide levels, and delivery of growth-promoting stimuli through cell transplantation and neurotrophic factor delivery. While all of these approaches have achieved varying degrees of improvement in plasticity, regeneration, and function, there is no clinically effective therapy for CNS injury. RNA interference technology offers strategies for improving regeneration by overcoming the aspects of the injured CNS environment that inhibit neurite growth. This occurs through the knockdown of growth-inhibitory molecules and their receptors. In this review, we discuss the current state of RNAi strategies for the treatment of CNS injury based on non-viral vector mediated delivery.<\/jats:p>","DOI":"10.1515\/rnan-2016-0003","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T07:22:34Z","timestamp":1472109754000},"source":"Crossref","is-referenced-by-count":3,"title":["Non-viral Vector Mediated RNA Interference Technology for Central Nervous System Injury"],"prefix":"10.3730","volume":"3","author":[{"given":"Christian","family":"Macks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeoung Soo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1320","reference":[{"key":"ref711","first-page":"142","article-title":"Neuroprotection by biodegradable PAMAM ester - mediated HMGB siRNA delivery in primary cortical culture and in the postischemic brain of Controlled Release","volume":"71","author":"Kim","year":"2010","journal-title":"Journal"},{"key":"ref411","first-page":"187","article-title":"da de Improving lipoplex - meidated gene transfer into C glioma cells and primary neurons","volume":"41","author":"Girao","year":"2004","journal-title":"Experimental Neurology"},{"key":"ref91","first-page":"417","article-title":"Nogo receptor agonist peptide promotes axonal regeration","volume":"10","author":"GrandPre","year":"2002","journal-title":"Nature"},{"key":"ref321","first-page":"440","article-title":"\u03b1 Accumulation and VEGF Expression","volume":"72","author":"1","year":"2007","journal-title":"Molecular Pharmacology"},{"key":"ref01","first-page":"865","article-title":"Rehabilitation Evidence Research Team A Systemic Review of the Effects of Pharmacological Agents on Walking Function in People with Spinal Cord","volume":"1","author":"Domingo","year":"2012","journal-title":"Spinal Cord Injury Injury Journal of Neurotrauma"},{"key":"ref751","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/nm1076","article-title":"RNAi suppresses polyglutamine - induced neurodegeneration in a model of spinocerebral ataxia","volume":"75","author":"Xia","year":"2004","journal-title":"Nature Medicine"},{"key":"ref721","first-page":"4","article-title":"Posttraumatic reduction of edema with aquaporin - RNA interference improves acute and chronic functional recovery of Blood","volume":"72","author":"Fukuda","year":"2013","journal-title":"Journal Cerebral Flow Metabolism"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1073\/pnas.0801775105","article-title":"Artificial miRNAs mitigate shRNA - mediated toxicity in the brain : Implications for the therapeutic development of RNAi","volume":"26","author":"McBride","year":"2008","journal-title":"PNAS"},{"key":"ref421","first-page":"99","article-title":"The role of helper lipids in lipid nanoparticles ( LNPs ) designed for oligonucleotide delivery","volume":"42","author":"Cheng","year":"2016","journal-title":"Advanced Drug Delivery Reviews"},{"key":"ref681","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1039\/C0CS00019A","article-title":"Cyclodextrin - based gene delivery systems","volume":"68","author":"Oritz Mellet","year":"2011","journal-title":"Chem Soc Rev"},{"key":"ref431","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-016-1527-4","article-title":"Donepezil loaded PEG nanoparticles : their ability to induce destabilization of amyloid fibrils and to cross blood brain barrier in vitro","volume":"43","author":"Baysal","year":"2016","journal-title":"J Neural Transm"},{"key":"ref591","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/S1359-6446(05)03573-7","article-title":"The role of nanobiotechnology in drug delivery","volume":"59","author":"Jain","year":"2005","journal-title":"Drug Discov Today"},{"key":"ref551","first-page":"1373","article-title":"Increased brain radioactivity by intranasal labeled siRNA dendriplexes within in situ - forming mucoadhesive gels","volume":"55","author":"Perez","year":"2012","journal-title":"International Journal of Nanomedicine"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"8876","DOI":"10.1523\/JNEUROSCI.22-20-08876.2002","article-title":"Truncated soluble Nogo binds Nogo - and blocks inhibition of axon growth by myelin","volume":"11","author":"Fournier","year":"2002","journal-title":"Neurosci"},{"key":"ref561","first-page":"1","article-title":"Non - Viral Nanosystems for Gene and Small Interfering RNA Delivery to the Central Nervous System : Formulating the Solution","volume":"56","author":"Mahony","year":"2013","journal-title":"Journal of Pharmaceutical Sciences"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/jgm.659","article-title":"Lipid - mediated siRNA delivery down - regulates exogenous gene expression in the mouse brain at picomolar levels","volume":"35","author":"Hassini","year":"2005","journal-title":"J Gene Med"},{"key":"ref371","first-page":"113","article-title":"de lipoplexes for neuronal siRNA delivery : A promising system to mediate gene silencing in the CNS of Controlled Release","volume":"37","author":"Cardoso Sim\u00f5es","year":"2008","journal-title":"Journal"},{"key":"ref741","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1101\/gad.981002","article-title":"Short hairpin RNAs ( shRNAs ) induce sequence - specific silencing in mammalian cells","volume":"74","author":"Paddison","year":"2002","journal-title":"Genes Development"},{"key":"ref641","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1006\/mcne.2001.1084","article-title":"Preferential transfection of adult mouse neural stem cells and their immediate progeny in vivo with polyethylenimine","volume":"64","author":"Lemkine","year":"2002","journal-title":"Mol Cell Neurosci"},{"key":"ref611","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1038\/mt.2011.35","article-title":"Pharmacological Characterization of Chemically Synthesized Monomeric phi pRNA Nanoparticles for Systemic Delivery","volume":"61","author":"Abdelmawla","year":"2011","journal-title":"Molecular Therapy"},{"key":"ref511","first-page":"241","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"51","author":"Alvarez","year":"2011","journal-title":"Nature Biotechnology"},{"key":"ref701","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1039\/b307062j","article-title":"Synthetic , self - assembly ABCD nanoparticles ; a structural paradigm for viable synthetic non - viral vectors","volume":"70","author":"Kostarelos","year":"2005","journal-title":"Chem Soc Rev"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1038\/nprot.2011.418","article-title":"Design and self - assembly of siRNA - functionalized RNA nanoparticles for use in automated nanomedicine","volume":"16","author":"Afonin","year":"2011","journal-title":"Nature Proc"},{"key":"ref71","first-page":"310","article-title":"EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans","volume":"8","author":"Koprivica","year":"2005","journal-title":"Science"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/jgm.1062","article-title":"Neuronspecific delivery of nucleic acids mediated by Tet - modified poly ( ethylenimine )","volume":"38","author":"Park","year":"2007","journal-title":"J Gene Med"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.addr.2012.08.008","article-title":"Exosomes for targeted siRNA delivery across biological barriers","volume":"50","author":"Andaloussi","year":"2013","journal-title":"Advanced Drug Delivery Reviews"},{"key":"ref621","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1089\/hum.1996.7.16-1947","article-title":"A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain","volume":"62","author":"Abdallah","year":"1996","journal-title":"Hum Gene Ther"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The elegans Heterochronic Gene lin - Encodes Small RNAs with Antisense Complementarity to lin -","volume":"20","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref141","first-page":"391","article-title":"Potent and specific genetic interference by double - stranded RNA in Caenorhabditic elegans","volume":"15","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"ref761","first-page":"87","article-title":"High - Efficiency Transfection of Short Hairpin RNAs - Encoding Plasmids Into Primary Hippocampal Neurons","volume":"76","author":"Zeitelhofer","year":"2009","journal-title":"Journal of Neuroscience Research"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0169-409X(00)00122-8","article-title":"Nanoparticulate systems for brain delivery of drugs","volume":"33","author":"Kreuter","year":"2001","journal-title":"Advanced Drug Delivery Reviews"},{"key":"ref21","first-page":"356","article-title":"Traumatic brain injury","volume":"3","author":"Ghajar","year":"2000","journal-title":"Lancet"},{"key":"ref571","first-page":"650","article-title":"Engineering RNA for Targeted siRNA Delivery and Medical Application","volume":"57","author":"Guo","year":"2011","journal-title":"Adv Drug Deliv Rev"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1021\/cn900029p","article-title":"- associated glycoprotein ( MAG ) protects neurons form acute toxicity using a ganglioside - dependent mechanism","volume":"6","author":"Mehta","year":"2010","journal-title":"ACS Chem Neurosci"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvescicles transport RNA and proteins that promote tumor growth and provide diagnostic biomarkers","volume":"53","author":"Skog","year":"2008","journal-title":"Nat Cell Bio"},{"key":"ref661","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.actbio.2016.02.013","article-title":"Cationic , amphiphilic nopolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord","volume":"66","author":"Gwak","year":"2016","journal-title":"Acta Biomaterialia"},{"key":"ref581","first-page":"1964","article-title":"Engineering , Assembly and Applications in Detection , Gene Delivery and Therapy","volume":"58","author":"Guo","year":"2005","journal-title":"RNA Nanotechnology Nanotechnol"},{"key":"ref161","first-page":"201","article-title":"Assembly of multifunctional phi pRNA nanoparticles for specific delivery of siRNA and other therapeutics to targeted cells","volume":"17","author":"Shu","year":"2011","journal-title":"Methods"},{"key":"ref41","first-page":"1","article-title":"Direct CNS Delivery of siRNA Mediates Robust Silencing in Oligodendrocytes XX","volume":"5","author":"Querbes","year":"2008","journal-title":"Oligonucleotides"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2174\/156720106776359230","article-title":"A review of nanocarrier - based CNS delivery systems","volume":"29","author":"Tiwari","year":"2006","journal-title":"Current Drug Delivery"},{"key":"ref241","first-page":"433","article-title":"Microarray analysis shows that some miRNAs downregulate large number of target mRNAs","volume":"25","author":"Lim","year":"2005","journal-title":"Nature"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00018-013-1310-8","article-title":"Novel siRNA delivery strategy : a new strand in CNS translational medicine ?","volume":"18","author":"Gherardini","year":"2014","journal-title":"Cell Mol Life Sci"},{"key":"ref441","first-page":"157","article-title":"rapid targeted , neuron - selective , in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain","volume":"44","author":"Nakajima","year":"2012","journal-title":"Journal of Biotechnology"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1474-4422(11)70286-1","article-title":"Non - coding RNAs with essential roles in neurodegenerative disorders","volume":"21","author":"Salta","year":"2012","journal-title":"Lancet Neurol"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3390\/ph6010085","article-title":"Nanoparticle - Based Delivery of RNAi Therapeutics : Progress and Challenges","volume":"34","author":"Zhou","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref81","first-page":"343","article-title":"Axon regeneration in rat spinal cord produced by an antibody against myelin - associated neurite growth inhibitors","volume":"9","author":"Scnell","year":"1990","journal-title":"Nature"},{"key":"ref471","first-page":"1","article-title":"Activation of different split functionalities on re - association of RNA - DNA hybrids","volume":"47","author":"Afonin","year":"2013","journal-title":"Nature Nanotechnology"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"10778","DOI":"10.1523\/JNEUROSCI.19-24-10778.1999","article-title":"The chondroitin sulfate proteo glycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar","volume":"7","author":"McKeon","year":"1999","journal-title":"Neurosci"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jddst.2015.07.007","article-title":"The fate of polymeric and lipid nanoparticles for brain delivery and targeting : Strategies and mechanism of blood - brain barrier crossing and trafficking into the central nervous system","volume":"40","author":"Tosi","year":"2016","journal-title":"Journal of Drug Delivery Science and Technology"},{"key":"ref631","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1073\/pnas.92.16.7297","article-title":"A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo : polyethylenimine","volume":"63","author":"Boussif","year":"1995","journal-title":"Proc Natl Acad Sci S"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.biomaterials.2013.09.068","article-title":"Differential nanotoxicological and neuroinflammatory liabilities of non - viral vectors for RNA interference in the central nervous system","volume":"54","author":"Godinho","year":"2014","journal-title":"Biomaterials"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1101\/gad.1262504","article-title":"The Drosha - DGCR complex in primary microRNA processing","volume":"23","author":"Han","year":"2004","journal-title":"Genes Development"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"11926","DOI":"10.1073\/pnas.182272699","article-title":"RNAi functions in cultured mammalian neurons","volume":"48","author":"Krichevsky","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1016\/j.biomaterials.2013.08.036","article-title":"Delivery of siRNA to the brain using a combination of nose - to - brain delivery and cell - penetrating peptide - modified nano - micelles","volume":"31","author":"Kanazawa","year":"2013","journal-title":"Biomaterials"},{"key":"ref651","first-page":"443","article-title":"Interfering with disease : a progress report on siRNA - based therapeutics","volume":"65","author":"Fougerolles","year":"2007","journal-title":"Nature Reviews"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"- mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"52","author":"Valadi","year":"2007","journal-title":"Nat Cell Biol"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"7689","DOI":"10.1093\/nar\/gkq645","article-title":"The terminal loop region controls microRNA processing by Drosha and Dicer","volume":"24","author":"Zhang","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.1021\/nn402662d","article-title":"Cyclic RGD - Linked Polymeric Micelles for Targeted Delivery of Platinum Anticancer Drugs to Glioblastoma through the Blood - Brain Tumor Barrier","volume":"39","author":"Miura","year":"2013","journal-title":"ACS Nano"},{"key":"ref451","first-page":"227","article-title":"Efficient and targeted delivery of siRNA in vivo","volume":"45","author":"Shim","year":"2010","journal-title":"FEBS Journal"},{"key":"ref11","first-page":"85","article-title":"Therapeutic Targets for Neuroprotection and \/ or Enhancement of Functional Recovery Following Traumatic Brain Injury Progress in Molecular Biology and","volume":"2","author":"Kelso","year":"2011","journal-title":"Translational Science"},{"key":"ref211","first-page":"425","article-title":"The nuclear RNase III Drosha initiates microRNA processing","volume":"22","author":"Lee","year":"2003","journal-title":"Nature"},{"key":"ref691","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.2217\/nnm.11.59","article-title":"Polycationic amphiphilic cyclodextrin - based nanoparticles for therapeutic gene delivery","volume":"69","author":"Mendez","year":"2011","journal-title":"Nanomedicine"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.4161\/cc.5.18.3192","article-title":"Delivery of RNA Interference","volume":"19","author":"Li","year":"2006","journal-title":"Cell Cycle"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s11095-006-9180-5","article-title":"Lipid - based Nanoparticles for Nucleic Acid Delivery","volume":"60","author":"Li","year":"2007","journal-title":"Pharm Res"},{"key":"ref731","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s13311-013-0183-8","article-title":"et al Recent Advances in RNA Interference Therapeutics for CNS Diseases","volume":"73","author":"Ramachandran","year":"2013","journal-title":"Neurotherapeutics"},{"key":"ref461","first-page":"213","article-title":"Bolaamphiphiles as Carriers for siRNA Delivery : From Syntheses to Practical Application of Controlled Release","volume":"46","author":"Gupta","year":"2015","journal-title":"Journal"},{"key":"ref491","first-page":"315","article-title":"Transfection of naked siRNA results in endosomal uptake and metabolic impairment in cultured neurons","volume":"49","author":"Lingor","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref361","first-page":"5995","article-title":"Investigation of enzyme - sensitive lipid nanoparticles for delivery of siRNA to blood - brain barrier and glioma cells","volume":"36","author":"Bruun","year":"2015","journal-title":"International Journal of Nanomedicine"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"7483","DOI":"10.1016\/j.biomaterials.2013.06.010","article-title":"Development of a gene \/ drug dual delivery system for brain tumor therapy : Potent inhibition via RNA interference and synergistic effects","volume":"28","author":"Lei","year":"2013","journal-title":"Biomaterials"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"15350","DOI":"10.1523\/JNEUROSCI.2510-13.2013","article-title":"Short Hairpin RNA against PTEN Enhances Regenerative Growth of Corticospinal Tract Axons after Spinal Cord","volume":"14","author":"Zukor","year":"2013","journal-title":"Injury Neurosci"}],"container-title":["DNA and RNA Nanotechnology"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/rnan.2016.3.issue-1\/rnan-2016-0003\/rnan-2016-0003.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/rnan-2016-0003\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T21:22:37Z","timestamp":1634073757000},"score":1,"resource":{"primary":{"URL":"http:\/\/access.portico.org\/stable?au=phxzf7jb9f"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,25]]},"references-count":70,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1515\/rnan-2016-0003","relation":{},"ISSN":["2353-1770"],"issn-type":[{"value":"2353-1770","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,25]]}}}