Since the first reports that double-stranded RNAs can efficiently silence gene expression in C . elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders.
References
[1]
Fire, X.S.; Montgomery, M.K.; Kostas, S.A.; Driver, S.E.; Mello, C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 19, 806–811.
[2]
Elbashir, S.M.; Lendeckel, W.; Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001, 15, 188–200, doi:10.1101/gad.862301.
[3]
Elbashir, S.M.; Harborth, J.; Lendeckel, W.; Yalcin, A.; Weber, K.; Tuschl, T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001, 411, 494–498, doi:10.1038/35078107.
[4]
U.S. National Institues of Health. Available online: http://www.ClinicalTrials.gov/ (accessed on 2 July 2013).
[5]
Xia, H.; Mao, Q.; Paulson, H.L.; Davidson, B.L. siRNA-mediated gene silencing in vitro and in vivo. Nat. Biotechnol. 2002, 20, 1006–1010.
[6]
Alves, S.; Nascimento-Ferreira, I.; Dufour, N.; Hassig, R.; Auregan, G.; Nobrega, C.; Brouillet, E.; Hantraye, P.; de Lima, M.C.P.; Déglon, N.; et al. Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: No role for wild-type ataxin-3? Hum. Mol. Genet. 2010, 19, 2380–2394, doi:10.1093/hmg/ddq111.
[7]
McBride, J.L.; Pitzer, M.R.; Boudreau, R.L.; Dufour, B.; Hobbs, T.; Ojeda, S.R.; Davidson, B.L. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington’s disease. Mol. Ther. 2011, 19, 2152–2162, doi:10.1038/mt.2011.219.
Hammond, S.M.; Bernstein, E.; Beach, D.; Hannon, G.J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 2000, 404, 293–296, doi:10.1038/35005107.
[10]
Bernstein, E.; Caudy, A.A.; Hammond, S.M.; Hannon, G.J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001, 409, 363–366, doi:10.1038/35053110.
[11]
Zamore, P.D.; Tuschl, T.; Sharp, P.A.; Bartel, D.P. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101, 25–33, doi:10.1016/S0092-8674(00)80620-0.
[12]
Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75, 843–854, doi:10.1016/0092-8674(93)90529-Y.
[13]
Chen, K.; Rajewsky, N. The evolution of gene regulation by transcription factors and microRNAs. Nat. Rev. Genet. 2007, 8, 93–103, doi:10.1038/nrg1990.
[14]
Manchester University. The miRBase. Available online: http://www.mirbase.org/cgi-bin/mirna_summary.pl?org=has/ (accessed on 2 July 2013).
[15]
Lee, Y.; Jeon, K.; Lee, J.T.; Kim, S.; Kim, V.N.; Micro, R.N. A maturation: Stepwise processing and subcellular localization. EMBO J. 2002, 21, 4663–4670, doi:10.1093/emboj/cdf476.
[16]
Cullen, B.R. Transcription and processing of human microRNA precursors. Mol. Cell. 2004, 16, 861–865, doi:10.1016/j.molcel.2004.12.002.
[17]
Knight, S.W.; Bass, B.L. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 2001, 293, 2269–2271, doi:10.1126/science.1062039.
[18]
Ketting, R.F.; Fischer, S.E.; Bernstein, E.; Sijen, T.; Hannon, G.J.; Plasterk, R.H. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001, 15, 2654–2659, doi:10.1101/gad.927801.
[19]
Tang, G. siRNA and miRNA: an insight into RISCs. Trends Biochem. Sci. 2005, 30, 106–114, doi:10.1016/j.tibs.2004.12.007.
[20]
Schwarz, D.S.; Hutvagner, G.; Du, T.; Xu, Z.; Aronin, N.; Zamore, P.D. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003, 115, 199–208, doi:10.1016/S0092-8674(03)00759-1.
[21]
Piao, X.; Zhang, X.; Wu, L.; Belasco, J.G. CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol. Cell. Biol. 2010, 30, 1486–1494, doi:10.1128/MCB.01481-09.
Boudreau, R.L.; Spengler, R.M.; Davidson, B.L. Rational design of therapeutic siRNAs: Minimizing off-targeting potential to improve the safety of RNAi therapy for Huntington’s disease. Mol. Ther. 2011, 19, 2169–2177, doi:10.1038/mt.2011.185.
[27]
Hohjoh, H. Enhancement of RNAi activity by improved siRNA duplexes. FEBS Lett. 2004, 557, 193–198, doi:10.1016/S0014-5793(03)01492-3.
[28]
Brummelkamp, T.R.; Bernards, R.; Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002, 19, 550–553, doi:10.1126/science.1068999.
[29]
Brummelkamp, T.R.; Bernards, R.; Agami, R. Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2002, 2, 243–247, doi:10.1016/S1535-6108(02)00122-8.
[30]
An, D.S.; Xie, Y.; Mao, S.H.; Morizono, K.; Kung, S.K.; Chen, I.S. Efficient lentiviral vectors for short hairpin RNA delivery into human cells. Hum. Gene Ther. 2003, 14, 1207–1212, doi:10.1089/104303403322168037.
[31]
Yu, J.Y.; DeRuiter, S.L.; Turner, D.L. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc. Natl. Acad. Sci. USA 2002, 99, 6047–6052, doi:10.1073/pnas.092143499.
[32]
Grimm, D.; Streetz, K.L.; Jopling, C.L.; Storm, T.A.; Pandey, K.; Davis, C.R.; Marion, P.; Salazar, F.; Kay, M.A. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 2006, 441, 537–541, doi:10.1038/nature04791.
[33]
Grimm, D.; Wang, L.; Lee, J.S.; Schurmann, N.; Gu, S.; Borner, K.; Storm, T.A.; Kay, M.A. Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver. J. Clin. Invest. 2010, 120, 3106–3119, doi:10.1172/JCI43565.
[34]
McBride, J.L.; Boudreau, R.L.; Harper, S.Q.; Staber, P.D.; Monteys, A.M.; Martins, I.; Gilmore, B.L.; Burstein, H.; Peluso, R.W.; Polisky, B.; et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi. Proc. Natl. Acad. Sci. USA 2008, 105, 5868–5873, doi:10.1073/pnas.0801775105.
[35]
Gou, D.; Narasaraju, T.; Chintagari, N.R.; Jin, N.; Wang, P.; Liu, L. Gene silencing in alveolar type II cells using cell-specific promoter in vitro and in vivo. Nucleic Acids Res. 2004, 32, e134, doi:10.1093/nar/gnh129.
[36]
Giering, J.C.; Grimm, D.; Storm, T.A.; Kay, M.A. Expression of shRNA From a Tissue-specific pol II Promoter Is an Effective and Safe RNAi Therapeutic. Mol. Ther. 2008, 16, 1630–1636, doi:10.1038/mt.2008.144.
[37]
Zhou, H.; Xia, X.G.; Xu, Z. An RNA polymerase II construct synthesizes short-hairpin RNA with a quantitative indicator and mediates highly efficient RNAi. Nucleic Acids Res. 2005, 33, e62, doi:10.1093/nar/gni061.
[38]
Stegmeier, F.; Hu, G.; Rickles, R.J.; Hannon, G.J.; Elledge, S.J. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells. Proc. Natl. Acad. Sci. USA 2005, 102, 13212–13217.
[39]
Silva, J.M.; Li, M.Z.; Chang, K.; Ge, W.; Golding, M.C.; Rickles, R.J.; Siolas, D.; Hu, G.; Paddison, P.J.; Schlabach, M.R.; et al. Second-generation shRNA libraries covering the mouse and human genomes. Nat. Genet. 2005, 37, 1281–1288.
[40]
Nielsen, T.T.; Marion, I.; Hasholt, L.; Lundberg, C. Neuron-specific RNA interference using lentiviral vectors. J. Gene Med. 2009, 11, 559–569.
[41]
Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005, 4, 145–160, doi:10.1038/nrd1632.
[42]
Akinc, A.; Zumbuehl, A.; Goldberg, M.; Leshchiner, E.S.; Busini, V.; Hossain, N.; Bacallado, S.A.; Nguyen, D.N.; Fuller, J.; Alvarez, R.; et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 2008, 26, 561–569, doi:10.1038/nbt1402.
[43]
Whitehead, K.A.; Langer, R.; Anderson, D.G. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 2009, 8, 129–138, doi:10.1038/nrd2742.
[44]
Hu-Lieskovan, S.; Heidel, J.D.; Bartlett, D.W.; Davis, M.E.; Triche, T.J. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’s sarcoma. Cancer Res. 2005, 65, 8984–8992, doi:10.1158/0008-5472.CAN-05-0565.
[45]
DiFiglia, M.; Sena-Esteves, M.; Chase, K.; Sapp, E.; Pfister, E.; Sass, M.; Yoder, J.; Reeves, P.; Pandey, R.K.; Rajeev, K.G.; et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl. Acad. Sci. USA 2007, 104, 17204–17209, doi:10.1073/pnas.0708285104.
[46]
Soutschek, J.; Akinc, A.; Bramlage, B.; Charisse, K.; Constien, R.; Donoghue, M.; Elbashir, S.; Geick, A.; Hadwiger, P.; Harborth, J.; et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004, 432, 173–178, doi:10.1038/nature03121.
[47]
Buchschacher, G.L., Jr. Introduction to retroviruses and retroviral vectors. Somat. Cell Mol. Genet. 2001, 26, 1–11, doi:10.1023/A:1021014728217.
[48]
Mann, R.; Mulligan, R.C.; Baltimore, D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 1983, 33, 153–159, doi:10.1016/0092-8674(83)90344-6.
[49]
Beyer, W.R.; Westphal, M.; Ostertag, W.; von Laer, D. Oncoretrovirus and lentivirus vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: Generation, concentration, and broad host range. J. Virol. 2002, 76, 1488–1495.
[50]
Hacein-Bey-Abina, S.; von Kalle, C.; Schmidt, M.; McCormack, M.P.; Wulffraat, N.; Leboulch, P.; Lim, A.; Osborne, C.S.; Pawliuk, R.; Morillon, E.; et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003, 302, 415–419, doi:10.1126/science.1088547.
[51]
Hacein-Bey-Abina, S.; Garrigue, A.; Wang, G.P.; Soulier, J.; Lim, A.; Morillon, E.; Clappier, E.; Caccavelli, L.; Delabesse, E.; Beldjord, K.; et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Invest. 2008, 118, 3132–3142, doi:10.1172/JCI35700.
[52]
Cronin, J.; Zhang, X.Y.; Reiser, J. Altering the tropism of lentiviral vectors through pseudotyping. Curr. Gene Ther. 2005, 5, 387–398, doi:10.2174/1566523054546224.
[53]
Bartz, S.R.; Vodicka, M.A. Production of high-titer human immunodeficiency virus type 1 pseudotyped with vesicular stomatitis virus glycoprotein. Methods 1997, 12, 337–342, doi:10.1006/meth.1997.0487.
[54]
Naldini, L.; Blomer, U.; Gallay, P.; Ory, D.; Mulligan, R.; Gage, F.H.; Verma, I.M.; Trono, D. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996, 272, 263–267.
[55]
Kahl, C.A.; Marsh, J.; Fyffe, J.; Sanders, D.A.; Cornetta, K. Human immunodeficiency virus type 1-derived lentivirus vectors pseudotyped with envelope glycoproteins derived from Ross River virus and Semliki Forest virus. J. Virol. 2004, 78, 1421–1430, doi:10.1128/JVI.78.3.1421-1430.2004.
[56]
Hong, C.S.; Goins, W.F.; Goss, J.R.; Burton, E.A.; Glorioso, J.C. Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer’s disease-related amyloid-beta peptide in vivo. Gene Ther. 2006, 13, 1068–1079, doi:10.1038/sj.gt.3302719.
[57]
Dong, J.Y.; Fan, P.D.; Frizzell, R.A. Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum. Gene Ther. 1996, 7, 2101–2112, doi:10.1089/hum.1996.7.17-2101.
[58]
Kotin, R.M.; Siniscalco, M.; Samulski, R.J.; Zhu, X.D.; Hunter, L.; Laughlin, C.A.; McLaughlin, S.; Muzyczka, N.; Rocchi, M.; Berns, K.I. Site-specific integration by adeno-associated virus. Proc. Natl. Acad. Sci. USA 1990, 87, 2211–2215, doi:10.1073/pnas.87.6.2211.
[59]
Kotin, R.M.; Linden, R.M.; Berns, K.I. Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J. 1992, 11, 5071–5078.
[60]
Kaplitt, M.G.; Leone, P.; Samulski, R.J.; Xiao, X.; Pfaff, D.W.; O'Malley, K.L.; During, M.J. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 1994, 8, 148–154, doi:10.1038/ng1094-148.
[61]
McCown, T.J.; Xiao, X.; Li, J.; Breese, G.R.; Samulski, R.J. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res. 1996, 713, 99–107.
[62]
Samulski, R.J.; Berns, K.I.; Tan, M.; Muzyczka, N. Cloning of adeno-associated virus into pBR322: Rescue of intact virus from the recombinant plasmid in human cells. Proc. Natl. Acad. Sci. USA 1982, 79, 2077–2081, doi:10.1073/pnas.79.6.2077.
Weinberg, M.S.; Samulski, R.J.; McCown, T.J. Adeno-associated virus (AAV) gene therapy for neurological disease. Neuropharmacology 2013, 69, 82–88, doi:10.1016/j.neuropharm.2012.03.004.
[66]
Teichler, Z.D. US gene therapy in crisis. Trends Genet. 2000, 16, 272–275, doi:10.1016/S0168-9525(00)02025-4.
[67]
Cann, A. Principles of Molecular Virology, 3rd ed. ed.; Academic Press: Waltham, MA, USA, 2001.
[68]
Bukrinsky, M.I.; Haggerty, S.; Dempsey, M.P.; Sharova, N.; Adzhubel, A.; Spitz, L.; Lewis, P.; Goldfarb, D.; Emerman, M.; Stevenson, M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 1993, 365, 666–669, doi:10.1038/365666a0.
[69]
Emi, N.; Friedmann, T.; Yee, J.K. Pseudotype formation of murine leukemia virus with the G protein of vesicular stomatitis virus. J. Virol. 1991, 65, 1202–1207.
[70]
Kang, Y.; Stein, C.S.; Heth, J.A.; Sinn, P.L.; Penisten, A.K.; Staber, P.D.; Ratliff, K.L.; Shen, H.; Barker, C.K.; Martins, I. In vivo gene transfer using a nonprimate lentiviral vector pseudotyped with Ross River Virus glycoproteins. J. Virol. 2002, 76, 9378–9388.
[71]
Georgievska, B.; Kirik, D.; Bjorklund, A. Overexpression of glial cell line-derived neurotrophic factor using a lentiviral vector induces time- and dose-dependent downregulation of tyrosine hydroxylase in the intact nigrostriatal dopamine system. J. Neuro. Sci. 2004, 24, 6437–6445.
[72]
Deglon, N.; Tseng, J.L.; Bensadoun, J.C.; Zurn, A.D.; Arsenijevic, Y.; de Pereira, A.L.; Zufferey, R.; Trono, D.; Aebischer, P. Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson’s disease. Hum. Gene Ther. 2000, 11, 179–190, doi:10.1089/10430340050016256.
[73]
Jakobsson, J.; Nielsen, T.T.; Staflin, K.; Georgievska, B.; Lundberg, C. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors. Gene Ther. 2006, 13, 966–973, doi:10.1038/sj.gt.3302701.
[74]
Naldini, L.; Blomer, U.; Gage, F.H.; Trono, D.; Verma, I.M. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl. Acad. Sci. USA 1996, 93, 11382–11388.
[75]
Azzouz, M.; Le, T.; Ralph, G.S.; Walmsley, L.; Monani, U.R.; Lee, D.C.; Wilkes, F.; Mitrophanous, K.A.; Kingsman, S.M.; Burghes, A.H.; et al. Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy. J. Clin. Invest. 2004, 114, 1726–1731.
[76]
Azzouz, M.; Ralph, G.S.; Storkebaum, E.; Walmsley, L.E.; Mitrophanous, K.A.; Kingsman, S.M.; Carmeliet, P.; Mazarakis, N.D. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004, 429, 413–417, doi:10.1038/nature02544.
[77]
Powell, S.K.; Kaloss, M.A.; Pinkstaff, A.; McKee, R.; Burimski, I.; Pensiero, M.; Otto, E.; Stemmer, W.P.; Soong, N.W. Breeding of retroviruses by DNA shuffling for improved stability and processing yields. Nat. Biotechnol. 2000, 18, 1279–1282, doi:10.1038/82391.
[78]
Merten, C.A.; Stitz, J.; Braun, G.; Poeschla, E.M.; Cichutek, K.; Buchholz, C.J. Directed evolution of retrovirus envelope protein cytoplasmic tails guided by functional incorporation into lentivirus particles. J. Virol. 2005, 79, 834–840, doi:10.1128/JVI.79.2.834-840.2005.
[79]
Hwang, B.Y.; Schaffer, D.V. Engineering a serum-resistant and thermostable vesicular stomatitis virus G glycoprotein for pseudotyping retroviral and lentiviral vectors. Gene Ther. 2013, doi:10.1038/gt.2013.1.
[80]
Bell, P.; Wang, L.; Lebherz, C.; Flieder, D.B.; Bove, M.S.; Wu, D.; Gao, G.P.; Wilson, J.M.; Wivel, N.A. No evidence for tumorigenesis of AAV vectors in a large-scale study in mice. Mol. Ther. 2005, 12, 299–306, doi:10.1016/j.ymthe.2005.03.020.
Bell, P.; Moscioni, A.D.; McCarter, R.J.; Wu, D.; Gao, G.; Hoang, A.; Sanmiguel, J.C.; Sun, X.; Wivel, N.A.; Raper, S.E.; et al. Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver. Mol. Ther. 2006, 14, 34–44, doi:10.1016/j.ymthe.2006.03.008.
[83]
UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust. GOSH Announces Leukaemia Case Following Gene Therapy for X-SCID. Available online: http://www.ich.ucl.ac.uk/pressoffice/pressrelease_00591/ (accessed on 2 July 2013).
[84]
Weinberg, M.S.; Blake, B.L.; Samulski, R.J.; McCown, T.J. The influence of epileptic neuropathology and prior peripheral immunity on CNS transduction by rAAV2 and rAAV5. Gene Ther. 2011, 18, 961–968, doi:10.1038/gt.2011.49.
[85]
Dodiya, H.B.; Bjorklund, T.; Stansell, J., III; Mandel, R.J.; Kirik, D.; Kordower, J.H. Differential transduction following basal ganglia administration of distinct pseudotyped AAV capsid serotypes in nonhuman primates. Mol. Ther. 2010, 18, 579–587, doi:10.1038/mt.2009.216.
[86]
Hadaczek, P.; Kohutnicka, M.; Krauze, M.T.; Bringas, J.; Pivirotto, P.; Cunningham, J.; Bankiewicz, K. Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain. Hum. Gene Ther. 2006, 17, 291–302, doi:10.1089/hum.2006.17.291.
[87]
Markakis, E.A.; Vives, K.P.; Bober, J.; Leichtle, S.; Leranth, C.; Beecham, J.; Elsworth, J.D.; Roth, R.H.; Samulski, R.J.; Redmond, D.E., Jr. Comparative transduction efficiency of AAV vector serotypes 1–6 in the substantia nigra and striatum of the primate brain. Mol. Ther. 2010, 18, 588–593, doi:10.1038/mt.2009.286.
[88]
Masamizu, Y.; Okada, T.; Ishibashi, H.; Takeda, S.; Yuasa, S.; Nakahara, K. Efficient gene transfer into neurons in monkey brain by adeno-associated virus 8. Neuroreport 2010, 21, 447–451, doi:10.1097/WNR.0b013e328338ba00.
Klein, R.L.; Dayton, R.D.; Tatom, J.B.; Henderson, K.M.; Henning, P.P. AAV8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification method. Mol. Ther. 2008, 16, 89–96, doi:10.1038/sj.mt.6300331.
[91]
Harding, T.C.; Dickinson, P.J.; Roberts, B.N.; Yendluri, S.; Gonzalez-Edick, M.; Lecouteur, R.A.; Jooss, K.U. Enhanced gene transfer efficiency in the murine striatum and an orthotopic glioblastoma tumor model, using AAV-7- and AAV-8-pseudotyped vectors. Hum. Gene Ther. 2006, 17, 807–820, doi:10.1089/hum.2006.17.807.
[92]
Rahim, A.A.; Wong, A.M.; Hoefer, K.; Buckley, S.M.; Mattar, C.N.; Cheng, S.H.; Chan, J.K.; Cooper, J.D.; Waddington, S.N. Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system. FASEB J. 2011, 25, 3505–3518, doi:10.1096/fj.11-182311.
[93]
Schmidt, C. RNAi momentum fizzles as pharma shifts priorities. Nat. Biotechnol. 2011, 29, 93–94, doi:10.1038/nbt0211-93.
[94]
Wang, Y.L.; Liu, W.; Wada, E.; Murata, M.; Wada, K.; Kanazawa, I. Clinico-pathological rescue of a model mouse of Huntington’s disease by siRNA. Neurosci. Res. 2005, 53, 241–249, doi:10.1016/j.neures.2005.06.021.
[95]
Harper, S.Q.; Staber, P.D.; He, X.; Eliason, S.L.; Martins, I.H.; Mao, Q.; Yang, L.; Kotin, R.M.; Paulson, H.L.; Davidson, B.L. RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc. Natl. Acad. Sci. USA 2005, 19, 5820–5825.
[96]
Hu, J.; Matsui, M.; Gagnon, K.T.; Schwartz, J.C.; Gabillet, S.; Arar, K.; Wu, J.; Bezprozvanny, I.; Corey, D.R. Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs. Nat. Biotechnol. 2009, 27, 478–484, doi:10.1038/nbt.1539.
Hu, J.; Liu, J.; Corey, D.R. Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism. Chem. Biol. 2010, 17, 1183–1188, doi:10.1016/j.chembiol.2010.10.013.
[99]
Van Bilsen, P.H.; Jaspers, L.; Lombardi, M.S.; Odekerken, J.C.; Burright, E.N.; Kaemmerer, W.F. Identification and allele-specific silencing of the mutant huntingtin allele in Huntington’s disease patient-derived fibroblasts. Hum. Gene Ther. 2008, 19, 710–719, doi:10.1089/hum.2007.116.
[100]
Warby, S.C.; Montpetit, A.; Hayden, A.R.; Carroll, J.B.; Butland, S.L.; Visscher, H.; Collins, J.A.; Semaka, A.; Hudson, T.J.; Hayden, M.R. CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup. Am. J. Hum. Genet. 2009, 84, 351–366, doi:10.1016/j.ajhg.2009.02.003.
[101]
Pfister, E.L.; Kennington, L.; Straubhaar, J.; Wagh, S.; Liu, W.; DiFiglia, M.; Landwehrmeyer, B.; Vonsattel, J.P.; Zamore, P.D.; Aronin, N. Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington’s disease patients. Curr. Biol. 2009, 19, 774–778, doi:10.1016/j.cub.2009.03.030.
[102]
Xia, H.; Mao, Q.; Eliason, S.L.; Harper, S.Q.; Martins, I.H.; Orr, H.T.; Paulson, H.L.; Yang, L.; Kotin, R.M.; Davidson, B.L. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 2004, 10, 816–820, doi:10.1038/nm1076.
[103]
Nobrega, C.; Nascimento-Ferreira, I.; Onofre, I.; Albuquerque, D.; Hirai, H.; Deglon, N.; de Almeida, L.P. Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice. PLoS One 2013, 8, e52396, doi:10.1371/journal.pone.0052396.
Tsou, W.L.; Soong, B.W.; Paulson, H.L.; Rodriguez-Lebron, E. Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6. Neurobiol. Dis. 2011, 43, 533–542, doi:10.1016/j.nbd.2011.04.016.
[106]
Fountaine, T.M.; Wade-Martins, R. RNA interference-mediated knockdown of alpha-synuclein protects human dopaminergic neuroblastoma cells from MPP(+) toxicity and reduces dopamine transport. J. Neurosci. Res. 2007, 85, 351–363, doi:10.1002/jnr.21125.
[107]
Sapru, M.K.; Yates, J.W.; Hogan, S.; Jiang, L.; Halter, J.; Bohn, M.C. Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp. Neurol. 2006, 198, 382–390, doi:10.1016/j.expneurol.2005.12.024.
[108]
De Ynigo-Mojado, L.; Martin-Ruiz, I.; Sutherland, J.D. Efficient allele-specific targeting of LRRK2 R1441 mutations mediated by RNAi. PLoS One 2011, 6, e21352, doi:10.1371/journal.pone.0021352.
[109]
Sibley, C.R.; Seow, Y.; Curtis, H.; Weinberg, M.S.; Wood, M.J. Silencing of Parkinson’s disease-associated genes with artificial mirtron mimics of miR-1224. Nucleic. Acid. Res. 2012, 40, 9863–9875, doi:10.1093/nar/gks712.
[110]
Gorbatyuk, O.S.; Li, S.; Nash, K.; Gorbatyuk, M.; Lewin, A.S.; Sullivan, L.F.; Mandel, R.J.; Chen, W.; Meyers, C.; Manfredsson, F.P.; et al. In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration. Mol. Ther. 2010, 18, 1450–1457, doi:10.1038/mt.2010.115.
[111]
Horvath, L.; van Marion, I.; Tai, K.; Nielsen, T.T.; Lundberg, C. Knockdown of GAD67 protein levels normalizes neuronal activity in a rat model of Parkinson’s disease. J. Gene Med. 2011, 13, 188–197.
[112]
Ding, H.; Schwarz, D.S.; Keene, A.; Affar, E.; Fenton, L.; Xia, X.; Shi, Y.; Zamore, P.D.; Xu, Z.; et al. Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis. Aging Cell 2003, 2, 209–217, doi:10.1046/j.1474-9728.2003.00054.x.
[113]
Ralph, G.S.; Radcliffe, P.A.; Day, D.M.; Carthy, J.M.; Leroux, M.A.; Lee, D.C.; Wong, L.F.; Bilsland, L.G.; Greensmith, L.; Kingsman, S.M.; et al. Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nat. Med. 2005, 11, 429–433, doi:10.1038/nm1205.
[114]
Xia, X.; Zhou, H.; Huang, Y.; Xu, Z. Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo. Neurobiol. Dis. 2006, 23, 578–586, doi:10.1016/j.nbd.2006.04.019.
[115]
Towne, C.; Raoul, C.; Schneider, B.L.; Aebischer, P. Systemic AAV6 delivery mediating RNA interference against SOD1: Neuromuscular transduction does not alter disease progression in fALS mice. Mol. Ther. 2008, 16, 1018–1025, doi:10.1038/mt.2008.73.
[116]
Towne, C.; Setola, V.; Schneider, B.L.; Aebischer, P. Neuroprotection by gene therapy targeting mutant SOD1 in individual pools of motor neurons does not translate into therapeutic benefit in fALS mice. Mol. Ther. 2011, 19, 274–283, doi:10.1038/mt.2010.260.
[117]
Xie, Z.; Romano, D.M.; Kovacs, D.M.; Tanzi, R.E. Effects of RNA interference-mediated silencing of gamma-secretase complex components on cell sensitivity to caspase-3 activation. J. Biol. Chem. 2004, 279, 34130–34137.
[118]
Kandimalla, R.J.; Wani, W.Y.; Binukumar, B.K.; Gill, K.D. siRNA against presenilin 1 (PS1) down regulates amyloid beta42 production in IMR-32 cells. J. Biomed. Sci. 2012, 19, 2, doi:10.1186/1423-0127-19-2.
Jiang, Y.; Mullaney, K.A.; Peterhoff, C.M.; Che, S.; Schmidt, S.D.; Boyer-Boiteau, A.; Ginsberg, S.D.; Cataldo, A.M.; Mathews, P.M.; Nixon, R.A. Alzheimer’s-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition. Proc. Natl. Acad. Sci. USA 2010, 107, 1630–1635, doi:10.1073/pnas.0908953107.
[121]
Senechal, Y.; Prut, L.; Kelly, P.H.; Staufenbiel, M.; Natt, F.; Hoyer, D.; Wiessner, C.; Dev, K.K. Increased exploratory activity of APP23 mice in a novel environment is reversed by siRNA. Brain Res. 2008, 1243, 124–133, doi:10.1016/j.brainres.2008.09.024.
[122]
Singer, O.; Marr, R.A.; Rockenstein, E.; Crews, L.; Coufal, N.G.; Gage, F.H.; Verma, I.M.; Masliah, E. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat. Neurosci. 2005, 8, 1343–1349, doi:10.1038/nn1531.
[123]
Zheng, W.; Xin, N.; Chi, Z.H.; Zhao, B.L.; Zhang, J.; Li, J.Y.; Wang, Z.Y. Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation. FASEB J. 2009, 23, 4207–4217, doi:10.1096/fj.09-135749.
[124]
Piedrahita, D.; Hernandez, I.; Lopez-Tobon, A.; Fedorov, D.; Obara, B.; Manjunath, B.S.; Boudreau, R.L.; Davidson, B.; Laferla, F.; Gallego-Gomez, J.C.; et al. Silencing of CDK5 reduces neurofibrillary tangles in transgenic alzheimer’s mice. J. Neurosci. 2010, 30, 13966–13976, doi:10.1523/JNEUROSCI.3637-10.2010.
[125]
Nakahara, J.; Maeda, M.; Aiso, S.; Suzuki, N. Current concepts in multiple sclerosis: Autoimmunity versus oligodendrogliopathy. Clin. Rev. Allergy Immunol. 2012, 42, 26–34, doi:10.1007/s12016-011-8287-6.
[126]
Bueler, H.; Aguzzi, A.; Sailer, A.; Greiner, R.A.; Autenried, P.; Aguet, M.; Weissmann, C. Mice devoid of PrP are resistant to scrapie. Cell 1993, 73, 1339–1347, doi:10.1016/0092-8674(93)90360-3.
[127]
MacDonald, M.E.; Ambrose, C.M.; Duyao, M.P.; Myers, R.H.; Lin, C.; Srinidhi, L.; Barnes, G.; Taylor, S.A.; James, M.; Groot, N.; et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 1993, 72, 971–983, doi:10.1016/0092-8674(93)90585-E.
[128]
Ambrose, C.M.; Duyao, M.P.; Barnes, G.; Bates, G.P.; Lin, C.S.; Srinidhi, J.; Baxendale, S.; Hummerich, H.; Lehrach, H.; Altherr, M.; et al. Structure and expression of the Huntington’s disease gene: Evidence against simple inactivation due to an expanded CAG repeat. Somat. Cell. Mol. Genet. 1994, 20, 27–38, doi:10.1007/BF02257483.
[129]
Kowall, N.W.; Ferrante, R.J.; Martin, J.B. Patterns of cell loss in Huntington’s disease. Trends Neurosci. 1987, 10, 24–29, doi:10.1016/0166-2236(87)90120-2.
[130]
Rosas, H.D.; Liu, A.K.; Hersch, S.; Glessner, M.; Ferrante, R.J.; Salat, D.H.; van der Kouwe, A.; Jenkins, B.G.; Dale, A.M.; Fischl, B. Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology 2002, 58, 695–701, doi:10.1212/WNL.58.5.695.
[131]
Davies, S.W.; Turmaine, M.; Cozens, B.A.; DiFiglia, M.; Sharp, A.H.; Ross, C.A.; Scherzinger, E.; Wanker, E.E.; Mangiarini, L.; Bates, G.P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90, 537–548.
[132]
Palfi, S.; Brouillet, E.; Jarraya, B.; Bloch, J.; Jan, C.; Shin, M.; Conde, F.; Li, X.J.; Aebischer, P.; Hantraye, P.; et al. Expression of mutated huntingtin fragment in the putamen is sufficient to produce abnormal movement in non-human primates. Mol. Ther. 2007, 15, 1444–1451, doi:10.1038/sj.mt.6300185.
[133]
Wellington, C.L.; Ellerby, L.M.; Hackam, A.S.; Margolis, R.L.; Trifiro, M.A.; Singaraja, R.; McCutcheon, K.; Salvesen, G.S.; Propp, S.S.; Bromm, M.; et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem. 1998, 273, 9158–9167, doi:10.1074/jbc.273.15.9158.
[134]
Graham, R.K.; Deng, Y.; Slow, E.J.; Haigh, B.; Bissada, N.; Lu, G.; Pearson, J.; Shehadeh, J.; Bertram, L.; Murphy, Z.; et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 2006, 125, 1179–1191, doi:10.1016/j.cell.2006.04.026.
[135]
Bird, T.D. Hereditary Ataxia Overview; Bird, T.D., Pagon, R.A., Adam, M.P., Dolan, C.R., Fong, C.T., Stephens, K., Eds.; University of Washington: Seattle, WA, USA, 2012.
[136]
Jankovic, J. Parkinson’s disease: Clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 2008, 79, 368–376, doi:10.1136/jnnp.2007.131045.
[137]
Davie, C.A. A review of Parkinson’s disease. Br. Med. Bull. 2008, 86, 109–127, doi:10.1093/bmb/ldn013.
[138]
Cookson, M.R.; van der Brug, M. Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp. Neurol. 2008, 209, 5–11, doi:10.1016/j.expneurol.2007.05.022.
[139]
DeJesus-Hernandez, M.; Mackenzie, I.R.; Boeve, B.F.; Boxer, A.L.; Baker, M.; Rutherford, N.J.; Nicholson, A.M.; Finch, N.A.; Flynn, H.; Adamson, J.; et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011, 72, 245–256, doi:10.1016/j.neuron.2011.09.011.
[140]
Renton, A.E.; Majounie, E.; Waite, A.; Simon-Sanchez, J.; Rollinson, S.; Gibbs, J.R.; Schymick, J.C.; Laaksovirta, H.; van Swieten, J.C.; Myllykangas, L.; et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011, 72, 257–268, doi:10.1016/j.neuron.2011.09.010.
[141]
Chen, S.; Ge, X.; Chen, Y.; Lv, N.; Liu, Z.; Yuan, W. Advances with RNA interference in Alzheimer’s disease research. Drug Des. Dev. Ther. 2013, 7, 117–125.
[142]
Josephs, K.A.; Hodges, J.R.; Snowden, J.S.; Mackenzie, I.R.; Neumann, M.; Mann, D.M.; Dickson, D.W. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta. Neuropathol. 2011, 122, 137–153, doi:10.1007/s00401-011-0839-6.
[143]
Carta, A.R.; Fenu, S.; Pala, P.; Tronci, E.; Morelli, M. Selective modifications in GAD67 mRNA levels in striatonigral and striatopallidal pathways correlate to dopamine agonist priming in 6-hydroxydopamine-lesioned rats. Eur. J. Neurosci. 2003, 18, 2563–2572, doi:10.1046/j.1460-9568.2003.02983.x.
[144]
Bergman, H.; Deuschl, G. Pathophysiology of Parkinson’s disease: From clinical neurology to basic neuroscience and back. Mov. Disord. 2002, 17, S28–S40, doi:10.1002/mds.10140.
[145]
Winkler, C.; Bentlage, C.; Cenci, M.A.; Nikkhah, G.; Bjorklund, A. Regulation of neuropeptide mRNA expression in the basal ganglia by intrastriatal and intranigral transplants in the rat Parkinson model. Neuroscience 2003, 118, 1063–1077, doi:10.1016/S0306-4522(03)00007-1.
[146]
Soghomonian, J.J.; Gonzales, C.; Chesselet, M.F. Messenger RNAs encoding glutamate-decarboxylases are differentially affected by nigrostriatal lesions in subpopulations of striatal neurons. Brain Res. 1992, 576, 68–79, doi:10.1016/0006-8993(92)90610-L.
[147]
Wichmann, T.; DeLong, M.R. Pathophysiology of Parkinson’s disease: The MPTP primate model of the human disorder. Ann. N. Y. Acad. Sci. 2003, 991, 199–213, doi:10.1111/j.1749-6632.2003.tb07477.x.
[148]
Vila, M.; Levy, R.; Herrero, M.T.; Ruberg, M.; Faucheux, B.; Obeso, J.A.; Agid, Y.; Hirsch, E.C. Consequences of nigrostriatal denervation on the functioning of the basal ganglia in human and nonhuman primates: An in situ hybridization study of cytochrome oxidase subunit I mRNA. J. Neurosci. 1997, 17, 765–773.
[149]
Jakobsson, J.; Rosenqvist, N.; Marild, K.; Agoston, V.; Lundberg, C. Evidence for disease-regulated transgene expression in the brain with use of lentiviral vectors. J. Neurosci. Res. 2006, 84, 58–67, doi:10.1002/jnr.20872.
[150]
Voorn, P.; Roest, G.; Groenewegen, H.J. Increase of enkephalin and decrease of substance P immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions. Brain Res. 1987, 412, 391–396, doi:10.1016/0006-8993(87)91149-8.
Bueler, H.; Fischer, M.; Lang, Y.; Bluethmann, H.; Lipp, H.P.; de Armond, S.J.; Prusiner, S.B.; Aguet, M.; Weissmann, C. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 1992, 356, 577–582, doi:10.1038/356577a0.
[154]
Pfeifer, A.; Eigenbrod, S.; Al-Khadra, S.; Hofmann, A.; Mitteregger, G.; Moser, M.; Bertsch, U.; Kretzschmar, H. Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice. J. Clin. Invest. 2006, 116, 3204–3210, doi:10.1172/JCI29236.
