Journal of Molecular Medicine

, 89:1065 | Cite as

The miRNA pathway in neurological and skeletal muscle disease: implications for pathogenesis and therapy

  • Christopher R. Sibley
  • Matthew J. A. Wood


RNA interference (RNAi) represents a powerful post-transcriptional gene silencing network which fine-tunes gene expression in all eukaryotic cells. The endogenous triggers of RNAi, microRNAs (miRNAs), are proposed to regulate expression of up to a third of all protein-coding genes, and have been shown to have critical roles in developmental processes including in the central nervous system and skeletal muscle. Further, many have been reported to display differential expression in various disease states. Here we describe present understanding of the biogenesis and function of miRNAs, review current knowledge of miRNA abnormalities in both human neurological and skeletal muscle disease and discuss their potential as novel disease biomarkers. Finally, we highlight the many ways in which the miRNA pathway may be targeted for therapeutic benefit.


RNAi miRNA Neurodegeneration Myopathy Muscular dystrophy 



C.R.S. is supported by funding from Parkinson’s UK; M.J.A.W. is supported by funding from the UK MRC, The Wellcome Trust, Parkinson’s UK, the Muscular Dystrophy Campaign and Action Duchenne. The authors would like to thank Thomas Roberts for the critical reading of this manuscript.


  1. 1.
    Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811PubMedCrossRefGoogle Scholar
  2. 2.
    Erson AE, Petty EM (2008) MicroRNAs in development and disease. Clin Genet 74(4):296–306PubMedCrossRefGoogle Scholar
  3. 3.
    Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10):1902–1910PubMedCrossRefGoogle Scholar
  4. 4.
    Saini HK, Griffiths-Jones S, Enright AJ (2007) Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci U S A 104(45):17719–17724PubMedCrossRefGoogle Scholar
  5. 5.
    Han J et al (2006) Molecular basis for the recognition of primary microRNAs by the Drosha–DGCR8 complex. Cell 125(5):887–901PubMedCrossRefGoogle Scholar
  6. 6.
    Fukuda T et al (2007) DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol 9(5):604–611PubMedCrossRefGoogle Scholar
  7. 7.
    Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N (2007) Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins. Exp Cell Res 313(20):4196–4207PubMedCrossRefGoogle Scholar
  8. 8.
    Davis BN, Hilyard AC, Lagna G, Hata A (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454(7200):56–61PubMedCrossRefGoogle Scholar
  9. 9.
    Zeng Y, Cullen BR (2004) Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32(16):4776–4785PubMedCrossRefGoogle Scholar
  10. 10.
    Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U (2004) Nuclear export of microRNA precursors. Science 303(5654):95–98PubMedCrossRefGoogle Scholar
  11. 11.
    Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409(6818):363–366PubMedCrossRefGoogle Scholar
  12. 12.
    Chendrimada TP et al (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436(7051):740–744PubMedCrossRefGoogle Scholar
  13. 13.
    Rivas FV et al (2005) Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol 12(4):340–349PubMedCrossRefGoogle Scholar
  14. 14.
    Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7(7):719–723PubMedCrossRefGoogle Scholar
  15. 15.
    MacRae IJ, Ma E, Zhou M, Robinson CV, Doudna JA (2008) In vitro reconstitution of the human RISC-loading complex. Proc Natl Acad Sci U S A 105(2):512–517PubMedCrossRefGoogle Scholar
  16. 16.
    Meister G et al (2005) Identification of novel argonaute-associated proteins. Curr Biol 15(23):2149–2155PubMedCrossRefGoogle Scholar
  17. 17.
    Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115(2):209–216PubMedCrossRefGoogle Scholar
  18. 18.
    Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL (2008) The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. J Neurosci 28(53):14341–14346PubMedCrossRefGoogle Scholar
  19. 19.
    Gu S, Rossi JJ (2005) Uncoupling of RNAi from active translation in mammalian cells. RNA 11(1):38–44PubMedCrossRefGoogle Scholar
  20. 20.
    Zeng Y, Yi R, Cullen BR (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A 100(17):9779–9784PubMedCrossRefGoogle Scholar
  21. 21.
    Chendrimada TP et al (2007) MicroRNA silencing through RISC recruitment of eIF6. Nature 447(7146):823–828PubMedCrossRefGoogle Scholar
  22. 22.
    Humphreys DT, Westman BJ, Martin DIK, Preiss T (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 102(47):16961–16966PubMedCrossRefGoogle Scholar
  23. 23.
    Mathonnet G et al (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317(5845):1764–1767PubMedCrossRefGoogle Scholar
  24. 24.
    Petersen CP, Bordeleau M, Pelletier J, Sharp PA (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21(4):533–542PubMedCrossRefGoogle Scholar
  25. 25.
    Gu S, Jin L, Zhang F, Sarnow P, Kay MA (2009) Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs. Nat Struct Mol Biol 16(2):144–150PubMedCrossRefGoogle Scholar
  26. 26.
    Wu L, Fan J, Belasco JG (2006) MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 103(11):4034–4039PubMedCrossRefGoogle Scholar
  27. 27.
    Fabian MR et al (2009) Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol Cell 35(6):868–880PubMedCrossRefGoogle Scholar
  28. 28.
    Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15(2):185–197PubMedCrossRefGoogle Scholar
  29. 29.
    Lim LP et al (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433(7027):769–773PubMedCrossRefGoogle Scholar
  30. 30.
    Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21(6):1469–1477PubMedCrossRefGoogle Scholar
  31. 31.
    Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448PubMedCrossRefGoogle Scholar
  32. 32.
    Schratt GM et al (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289PubMedCrossRefGoogle Scholar
  33. 33.
    Weinberg MS, Wood MJA (2009) Short non-coding RNA biology and neurodegenerative disorders: novel disease targets and therapeutics. Hum Mol Genet 18(1):R27–R39PubMedCrossRefGoogle Scholar
  34. 34.
    Hébert SS et al (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 105(17):6415–6420PubMedCrossRefGoogle Scholar
  35. 35.
    Hébert SS et al (2009) MicroRNA regulation of Alzheimer's amyloid precursor protein expression. Neurobiol Dis 33(3):422–428PubMedCrossRefGoogle Scholar
  36. 36.
    Wang W et al (2008) The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 28(5):1213–1223PubMedCrossRefGoogle Scholar
  37. 37.
    Cogswell J et al (2008) Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14(1):27–41PubMedGoogle Scholar
  38. 38.
    Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283(46):31315–31322PubMedCrossRefGoogle Scholar
  39. 39.
    Wang W, Huang Q, Hu Y, Stromberg AJ, Nelson PT (2011) Patterns of microRNA expression in normal and early Alzheimer's disease human temporal cortex: white matter versus gray matter. Acta Neuropathol 121(2):193–205PubMedCrossRefGoogle Scholar
  40. 40.
    Nelson PT, Wang W (2010) MiR-107 is reduced in Alzheimer's disease brain neocortex: validation study. J Alzheimer's Dis 21(1):75–79Google Scholar
  41. 41.
    Shioya M et al (2010) Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator. Neuropathol Appl Neurobiol 36(4):320–330PubMedCrossRefGoogle Scholar
  42. 42.
    Kim J et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317(5842):1220–1224PubMedCrossRefGoogle Scholar
  43. 43.
    Perkins DO et al (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8(2):R27PubMedCrossRefGoogle Scholar
  44. 44.
    Zhu Y, Kalbfleisch T, Brennan M, Li Y (2009) A MicroRNA gene is hosted in an intron of a schizophrenia-susceptibility gene. Schizophr Res 109:86–89PubMedCrossRefGoogle Scholar
  45. 45.
    Beveridge NJ et al (2008) Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genetics 17(8):1156–1168CrossRefGoogle Scholar
  46. 46.
    Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ (2010) Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15(12):1176–1189PubMedCrossRefGoogle Scholar
  47. 47.
    Abu-Elneel K et al (2008) Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics 9(3):153–161PubMedCrossRefGoogle Scholar
  48. 48.
    Rossner S, Apelt J, Schliebs R, Perez-Polo JR, Bigl V (2001) Neuronal and glial beta-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology. J Neurosci Res 64(5):437–446PubMedCrossRefGoogle Scholar
  49. 49.
    Hartlage-Rübsamen M, Zeitschel U, Apelt J, Gärtner U, Franke H, Stahl T, Günther A, Schliebs R, Penkowa M, Bigl V, Rossner S (2003) Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent. Glia 41(2):169–179PubMedCrossRefGoogle Scholar
  50. 50.
    Kaltschmidt B, Uherek M, Volk B, Baeuerle PA, Kaltschmidt C (1997) Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc Natl Acad Sci U S A 94(6):2642–2647PubMedCrossRefGoogle Scholar
  51. 51.
    Mott JL, Kurita S, Cazanave SC, Bronk SF, Werneburg NW, Fernandez-Zapico ME (2010) Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. J Cell Biochem 110(5):1155–1164PubMedCrossRefGoogle Scholar
  52. 52.
    Curtale G et al (2009) An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood 115(2):265–273PubMedCrossRefGoogle Scholar
  53. 53.
    Hodges A et al (2006) Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 15(6):965–977PubMedCrossRefGoogle Scholar
  54. 54.
    Zuccato C et al (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 35(1):76–83PubMedCrossRefGoogle Scholar
  55. 55.
    Bithell A, Johnson R, Buckley NJ (2009) Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease. Biochem Soc Trans 37(6):1270–1275PubMedCrossRefGoogle Scholar
  56. 56.
    Persengiev S, Kondova I, Otting N, Koeppen AH, Bontrop RE (2010) Genome-wide analysis of miRNA expression reveals a potential role for miR-144 in brain aging and spinocerebellar ataxia pathogenesis. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2010.03.014
  57. 57.
    Margis R, Margis R, Rieder CRM (2011) Identification of blood microRNAs associated to Parkinsońs disease. J Biotechnol 152(3):96–101PubMedCrossRefGoogle Scholar
  58. 58.
    Wang G et al (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am J Hum Genet 82(2):283–289PubMedCrossRefGoogle Scholar
  59. 59.
    Rideout HJ, Dietrich P, Savalle M, Dauer WT, Stefanis L (2003) Regulation of alpha-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons. J Neurochem 84(4):803–813PubMedCrossRefGoogle Scholar
  60. 60.
    Abelson JF et al (2005) Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310(5746):317–320PubMedCrossRefGoogle Scholar
  61. 61.
    Rademakers R et al (2008) Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet 17(23):3631–3642PubMedCrossRefGoogle Scholar
  62. 62.
    Jensen KP, Covault J, Conner TS, Tennen H, Kranzler HR, Furneaux HM (2009) A common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors. Mol Psychiatry 14(4):381–389PubMedCrossRefGoogle Scholar
  63. 63.
    Cantuti-Castelvetri I, Keller-McGandy C, Bouzou B, Asteris G, Clark TW, Frosch MP, Standaert DG (2007) Effects of gender on nigral gene expression and parkinson disease. Neurobiol Dis 26(3):606–614PubMedCrossRefGoogle Scholar
  64. 64.
    Hoefig KP, Heissmeyer V (2010) Measuring microRNA expression in size-limited FACS-sorted and microdissected samples. Methods Mol Biol 667:47–63PubMedCrossRefGoogle Scholar
  65. 65.
    Latronico MVG, Condorelli G (2009) MicroRNAs and cardiac pathology. Nat Rev Cardiol 6(6):419–429PubMedCrossRefGoogle Scholar
  66. 66.
    Le Grand F, Rudnicki MA (2007) Skeletal muscle satellite cells and adult myogenesis. Curr Opin Cell Biol 19(6):628–633PubMedCrossRefGoogle Scholar
  67. 67.
    Kassar-Duchossoy L et al (2004) Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature 431(7007):466–471PubMedCrossRefGoogle Scholar
  68. 68.
    Li S et al (2005) Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice. Proc Natl Acad Sci U S A 102(4):1082–1087PubMedCrossRefGoogle Scholar
  69. 69.
    Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF (2006) Myogenic factors that regulate expression of muscle-specific microRNAs. Proc Natl Acad Sci U S A 103(23):8721–8726PubMedCrossRefGoogle Scholar
  70. 70.
    Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048):214–220PubMedCrossRefGoogle Scholar
  71. 71.
    Soulez M et al (1996) Growth and differentiation of C2 myogenic cells are dependent on serum response factor. Mol Cell Biol 16(11):6065–6074PubMedGoogle Scholar
  72. 72.
    Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38(2):228–233PubMedCrossRefGoogle Scholar
  73. 73.
    Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A (2006) Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174(5):677–687PubMedCrossRefGoogle Scholar
  74. 74.
    Anderson C, Catoe H, Werner R (2006) MIR-206 regulates connexin43 expression during skeletal muscle development. Nucleic Acids Res 34(20):5863–5871PubMedCrossRefGoogle Scholar
  75. 75.
    McKinsey TA, Zhang CL, Lu J, Olson EN (2000) Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408(6808):106–111PubMedCrossRefGoogle Scholar
  76. 76.
    Lu J, McKinsey TA, Zhang CL, Olson EN (2000) Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 6(2):233–244PubMedCrossRefGoogle Scholar
  77. 77.
    Eisenberg I et al (2007) Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci U S A 104(43):17016–17021PubMedCrossRefGoogle Scholar
  78. 78.
    Jindra PT, Bagley J, Godwin JG, Iacomini J (2010) Costimulation-dependent expression of microRNA-214 increases the ability of T cells to proliferate by targeting Pten. J Immunol 185(2):990–997PubMedCrossRefGoogle Scholar
  79. 79.
    Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009) miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 1792(6):497–505PubMedGoogle Scholar
  80. 80.
    Marotta M, Sarria Y, Ruiz-Roig C, Munell F, Roig-Quilis M (2007) Laser microdissection-based expression analysis of key genes involved in muscle regeneration in mdx mice. Neuromuscul Disord 17(9–10):707–718PubMedCrossRefGoogle Scholar
  81. 81.
    Miyachi M et al (2010) Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys Res Commun 400(1):89–93PubMedCrossRefGoogle Scholar
  82. 82.
    Greco S et al (2009) Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia. FASEB J 23(10):3335–3346PubMedCrossRefGoogle Scholar
  83. 83.
    Cacchiarelli D et al (2011) miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy. EMBO Rep 12(2):136–141PubMedCrossRefGoogle Scholar
  84. 84.
    Gambardella S et al (2010) Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients. J Translational Med 8:48CrossRefGoogle Scholar
  85. 85.
    Carey KA et al (2006) Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays. Pathol Int 56(5):246–255PubMedCrossRefGoogle Scholar
  86. 86.
    Williams AH et al (2009) MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326(5959):1549–1554PubMedCrossRefGoogle Scholar
  87. 87.
    Mitchell PS et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518PubMedCrossRefGoogle Scholar
  88. 88.
    Ali S, Almhanna K, Chen W, Philip PA, Sarkar FH (2010) Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer. Am J Translational Res 3(1):28–47Google Scholar
  89. 89.
    Doench JG, Petersen CP, Sharp PA (2003) siRNAs can function as miRNAs. Genes Dev 17(4):438–442PubMedCrossRefGoogle Scholar
  90. 90.
    Bader AG, Brown D, Winkler M (2010) The promise of microRNA replacement therapy. Cancer Res 70(18):7027–7030PubMedCrossRefGoogle Scholar
  91. 91.
    Singer O et al (2005) Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci 8(10):1343–1349PubMedCrossRefGoogle Scholar
  92. 92.
    Hong C, Goins WF, Goss JR, Burton EA, Glorioso JC (2006) Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-beta peptide in vivo. Gene Ther 13(14):1068–1079PubMedCrossRefGoogle Scholar
  93. 93.
    Kaplitt MG et al (2007) Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 369(9579):2097–2105PubMedCrossRefGoogle Scholar
  94. 94.
    Christine CW et al (2009) Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73(20):1662–1669PubMedCrossRefGoogle Scholar
  95. 95.
    Roberds SL et al (2001) BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum Mol Genet 10(12):1317–1324PubMedCrossRefGoogle Scholar
  96. 96.
    Zheng H et al (1995) beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81(4):525–531PubMedCrossRefGoogle Scholar
  97. 97.
    Steinbach JP, Müller U, Leist M, Li ZW, Nicotera P, Aguzzi A (1998) Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ 5(10):858–866PubMedCrossRefGoogle Scholar
  98. 98.
    Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4(9):721–726PubMedCrossRefGoogle Scholar
  99. 99.
    Krützfeldt J et al (2005) Silencing of microRNAs in vivo with 'antagomirs'. Nature 438(7068):685–689PubMedCrossRefGoogle Scholar
  100. 100.
    Choi W, Giraldez AJ, Schier AF (2007) Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318(5848):271–274PubMedCrossRefGoogle Scholar
  101. 101.
    Scherr M et al (2007) Lentivirus-mediated antagomir expression for specific inhibition of miRNA function. Nucleic Acids Res 35(22):e149PubMedCrossRefGoogle Scholar
  102. 102.
    Krützfeldt J et al (2007) Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 35(9):2885–2892PubMedCrossRefGoogle Scholar
  103. 103.
    Davis S, Lollo B, Freier S, Esau C (2006) Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res 34(8):2294–2304PubMedCrossRefGoogle Scholar
  104. 104.
    Elmén J et al (2008) LNA-mediated microRNA silencing in non-human primates. Nature 452(7189):896–899PubMedCrossRefGoogle Scholar
  105. 105.
    Fabani MM, Gait MJ (2008) miR-122 targeting with LNA/2'-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA-peptide conjugates. RNA 14(2):336–346PubMedCrossRefGoogle Scholar
  106. 106.
    Fabani MM et al (2010) Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Res 38(13):4466–4475PubMedCrossRefGoogle Scholar
  107. 107.
    Ivanova GD et al (2008) PNA-peptide conjugates as intracellular gene control agents. Nucleic Acids Symp Ser (Oxf) (52):31–32Google Scholar
  108. 108.
    Yin H et al (2010) Optimization of peptide nucleic acid antisense oligonucleotides for local and systemic dystrophin splice correction in the mdx mouse. Mol Ther: J Am Soc Gene Ther 18(4):819–827Google Scholar
  109. 109.
    Wu B et al (2008) Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci U S A 105(39):14814–14819PubMedCrossRefGoogle Scholar
  110. 110.
    Wu B et al (2010) Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino. Gene Ther 17(1):132–140PubMedCrossRefGoogle Scholar
  111. 111.
    Yin H et al (2009) A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum Mol Genet 18(22):4405–4414PubMedCrossRefGoogle Scholar
  112. 112.
    Yin H et al (2010) Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO. Mol Ther 18(10):1822–1829PubMedCrossRefGoogle Scholar
  113. 113.
    Sibley CR, Seow Y, Wood MJA (2010) Novel RNA-based strategies for therapeutic gene silencing. Mol Ther 18(3):466–476PubMedCrossRefGoogle Scholar
  114. 114.
    Ralph GS et al (2005) Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nat Med 11(4):429–433PubMedCrossRefGoogle Scholar
  115. 115.
    Raoul C et al (2005) Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nat Med 11(4):423–428PubMedCrossRefGoogle Scholar
  116. 116.
    Xia H et al (2004) RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 10(8):816–820PubMedCrossRefGoogle Scholar
  117. 117.
    Boudreau RL et al (2009) Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol Ther 17(6):1053–1063PubMedCrossRefGoogle Scholar
  118. 118.
    Kumar P et al (2007) Transvascular delivery of small interfering RNA to the central nervous system. Nature 448(7149):39–43PubMedCrossRefGoogle Scholar
  119. 119.
    Xia C, Zhang Y, Zhang Y, Boado RJ, Pardridge WM (2007) Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology. Pharmaceutical Res 24(12):2309–2316CrossRefGoogle Scholar
  120. 120.
    Zhang Y, Boado RJ, Pardridge WM (2003) In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J Gene Med 5(12):1039–1045PubMedCrossRefGoogle Scholar
  121. 121.
    Bonoiu AC et al (2009) Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons. Proc Natl Acad Sci U S A 106(14):5546–5550PubMedCrossRefGoogle Scholar
  122. 122.
    Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Exosome-mediated targeted systemic delivery of siRNA to the brain. Nat Biotechnol 29(4):341–345PubMedCrossRefGoogle Scholar
  123. 123.
    Fardaei M et al (2002) Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells. Hum Mol Genet 11(7):805–814PubMedCrossRefGoogle Scholar
  124. 124.
    Meola G, Moxley RT (2004) Myotonic dystrophy type 2 and related myotonic disorders. J Neurology 251(10):1173–1182CrossRefGoogle Scholar
  125. 125.
    Wheeler TM et al (2009) Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA. Science 325(5938):336–339PubMedCrossRefGoogle Scholar
  126. 126.
    Langlois M et al (2005) Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells. J Biological Chem 280(17):16949–16954CrossRefGoogle Scholar
  127. 127.
    Bostick B, Ghosh A, Yue Y, Long C, Duan D (2007) Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration. Gene Ther 14(22):1605–1609PubMedCrossRefGoogle Scholar
  128. 128.
    Yue Y et al (2008) A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs. Mol Ther 16(12):1944–1952PubMedCrossRefGoogle Scholar
  129. 129.
    Kinouchi N et al (2008) Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass. Gene Ther 15(15):1126–1130PubMedCrossRefGoogle Scholar
  130. 130.
    Honma K et al (2001) Atelocollagen-based gene transfer in cells allows high-throughput screening of gene functions. Bioch Biophys Res Commun 289(5):1075–1081CrossRefGoogle Scholar

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK

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