Targeting several CAG expansion diseases by a single antisense oligonucleotide

PLoS ONE

Volumn 6, Issue 9, 2011, Pages

  Evers, Melvin M ^a   Pepers, Barry A ^a   van Deutekom, Judith C T ^b   Mulders, Susan A M ^b   den Dunnen, Johan T ^a   Aartsma Rus, Annemieke ^a   van Ommen, Gert Jan B ^a   van Roon Mom, Willeke M C ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b Prosensa Therapeutics BV   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

2' O METHYL PHOSPHOROTHIOATE; ANDROGEN RECEPTOR; ANTISENSE OLIGONUCLEOTIDE; ATAXIN 1; ATAXIN 2; BINDING PROTEIN; HUNTINGTIN; MESSENGER RNA; UNCLASSIFIED DRUG; ATAXIN-1; ATXN3 PROTEIN, HUMAN; HD PROTEIN, HUMAN; MUTANT PROTEIN; NERVE PROTEIN; NUCLEAR PROTEIN; PEPTIDE; POLYGLUTAMINE; REPRESSOR PROTEIN;

ARTICLE; CAG REPEAT; CONTROLLED STUDY; DENTATORUBROPALLIDOLUYSIAN ATROPHY; DRUG ACTIVITY; FIBROBLAST; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; LYMPHOBLAST; PROTEIN TARGETING; SPINOCEREBELLAR DEGENERATION; CELL LINE; DEGENERATIVE DISEASE; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOLECULARLY TARGETED THERAPY; MYOCLONUS EPILEPSY; PATHOLOGY; TRINUCLEOTIDE REPEAT;

CELL LINE; FIBROBLASTS; GENE EXPRESSION REGULATION; HUMANS; MOLECULAR TARGETED THERAPY; MUTANT PROTEINS; MYOCLONIC EPILEPSIES, PROGRESSIVE; NERVE TISSUE PROTEINS; NEURODEGENERATIVE DISEASES; NUCLEAR PROTEINS; OLIGONUCLEOTIDES, ANTISENSE; PEPTIDES; REPRESSOR PROTEINS; RNA, MESSENGER; SPINOCEREBELLAR ATAXIAS; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 80052383976     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0024308     Document Type: Article

References (67)

1. Cummings CJ, Zoghbi HY, (2000) Fourteen and counting: unraveling trinucleotide repeat diseases. Hum Mol Genet 9: 909-916.
2. Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, et al. (2001) SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 10: 1441-1448.
3. Bauer PO, Nukina N, (2009) The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies. J Neurochem 110: 1737-1765.
4. Ranen NG, Stine OC, Abbott MH, Sherr M, Codori AM, et al. (1995) Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am J Hum Gen 57: 593-602.
5. Mcneil SM, Novelletto A, Srinidhi J, Barnes G, Kornbluth I, et al. (1997) Reduced penetrance of the Huntington's disease mutation. Hum Mol Genet 6: 775-779.
6. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, et al. (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington disease. Am J Hum Gen 53: 1118.
7. Huang CC, Faber PW, Persichetti F, Mittal V, Vonsattel JP, et al. (1998) Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins. Somat Cell Molec Gen 24: 217-233.
8. Muchowski PJ, Ning K, D'Souza-Schorey C, Fields S, (2002) Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. P Natl Acad Sci USA 99: 727-732.
9. Roon-Mom WMC, Reid SJ, Jones AL, MacDonald ME, Faull RLM, et al. (2002) Insoluble TATA-binding protein accumulation in Huntington's disease cortex. Mol Brain Res 109: 1-10.
10. Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, et al. (2000) The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. P Natl Acad Sci USA 97: 6763-6768.
11. Ross CA, Tabrizi SJ, (2011) Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10: 83-98.
12. Manto MU, (2005) The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 4: 2-6.
13. Schols L, Bauer P, Schmidt T, Schulte T, Riess O, (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3: 443.
14. Matilla-Duenas A, Goold R, Giunti P, (2008) Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum 7: 106-114.
15. Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, et al. (1998) Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95: 41-53.
16. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, et al. (1994) CAG expansions in a novel gene for Machado-Joseph Disease at chromosome 14Q32.1. Nat Genet 8: 221-228.
17. Padiath QS, Srivastava AK, Roy S, Jain S, Brahmachari SK, (2005) Identification of a novel 45 repeat unstable allele associated with a disease phenotype at the MJD1/SCA3 locus. Am J Med Genet B 133B: 124-126.
18. Riess O, Rub U, Pastore A, Bauer P, Schols L, (2008) SCA3: Neurological features, pathogenesis and animal models. Cerebellum 7: 125-137.
19. Shen Y, Peterson AS, (2009) Atrophins' emerging roles in development and neurodegenerative disease. Cell Mol Life Sci 66: 437-446.
20. Nagafuchi S, Yanagisawa H, Ohsaki E, Shirayama T, Tadokoro K, et al. (1994) Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). Nature Genet 8: 177-182.
21. Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, et al. (2006) Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125: 1179-1191.
22. Seo H, Sonntag KC, Kim W, Cattaneo E, Isacson O, (2007) Proteasome activator enhances survival of Huntington's disease neuronal model cells. PLoS ONE 2: e238.
23. Metcalf DJ, Garcia-Arencibia M, Hochfeld WE, Rubinsztein DC, (2010) Autophagy and misfolded proteins in neurodegeneration. Exp Neurol.
24. Scholefield J, Wood MJA, (2010) Therapeutic gene silencing strategies for polyglutamine disorders. Trends Genet 26: 29-38.
25. Rao DD, Senzer N, Cleary MA, Nemunaitis J, (2009) Comparative assessment of siRNA and shRNA off target effects: what is slowing clinical development. Cancer Gene Ther 16: 807-809.
26. Ding SW, Voinnet O, (2007) Antiviral immunity directed by small RNAs. Cell 130: 413-426.
27. Drouet V, Perrin V, Hassig R, Dufour N, Auregan G, et al. (2009) Sustained Effects of Nonallele-Specific Huntingtin Silencing. Ann Neurol 65: 276-285.
28. Dragatsis I, Levine MS, Zeitlin S, (2000) Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet 26: 300-306.
29. Zhang S, Feany MB, Saraswati S, Littleton JT, Perrimon N, (2009) Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's disease model. Dis Model Mech 2: 247-266.
30. van Bilsen PHJ, Jaspers L, Lombardi MS, Odekerken JCE, Burright EN, et al. (2008) Identification and allele-specific silencing of the mutant huntingtin allele in Huntington's disease patient-derived fibroblasts. Hum Gene Ther 19: 710-718.
31. Krol J, Fiszer A, Mykowska A, Sobczak K, de Mezer M, et al. (2007) Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Mol Cell 25: 575-586.
32. McBride JL, Boudreau RL, Harper SQ, Staber PD, Monteys AM, et al. (2008) Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi. P Natl Acad Sci USA 105: 5868-5873.
33. Robberecht W, (2000) Genetics of amyotrophic lateral sclerosis. J Neurol 247 (Suppl 6): VI/2-VI/6.
34. Smith RA, Miller TM, Yamanaka K, Monia BP, Condon TF, et al. (2006) Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest 116: 2290-2296.
35. ClinicalTrials.gov (2009) Safety,tolerability,and activity study of ISIS SOD1Rx to treat familial Amyotrophic Lateral Sclerosis (ALS) caused by SOD1 gene mutations (SOD-1). NCT01041222.
36. Gagnon KT, Pendergraff HM, Deleavey GF, Swayze EE, Potier P, et al. (2010) Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Biochemistry 49: 10166-10178.
37. Hu J, Gagnon KT, Liu J, Watts JK, Syeda-Nawaz J, et al. (2011) Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs. Biol Chem 392: 315-325.
38. Hu JX, Matsui M, Gagnon KT, Schwartz JC, Gabillet S, et al. (2009) Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs. Nat Biotechnol 27: 478-484.
39. Hu JX, Matsui M, Corey DR, (2009) Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA. Ann N Y Acad Sci 1175: 24-31.
40. Trottier Y, Devys D, Imbert G, Saudou F, An I, et al. (1995) Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form. Nat Genet 10: 104-110.
41. Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, et al. (1995) Polyglutamine expansion as a pathological epitope in Huntington's disease and 4 dominant cerebellar ataxias. Nature 378: 403-406.
42. Molla M, Delcher A, Sunyaev S, Cantor C, Kasif S, (2009) Triplet repeat length bias and variation in the human transcriptome. P Natl Acad Sci USA 106: 17095-17100.
43. Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A, (1995) Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat Genet 11: 155-163.
44. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, et al. (2001) Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci 24: 182-188.
45. Cattaneo E, Zuccato C, Tartari M, (2005) Normal huntingtin function: An alternative approach to Huntington's disease. Nat Rev Neurosci 6: 919-930.
46. Rigamonti D, Bauer JH, De Fraja C, Conti L, Sipione S, et al. (2000) Wild-type Huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 20: 3705-3713.
47. Sarkar S, Davies JE, Huang ZB, Tunnacliffe A, Rubinsztein DC, (2007) Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem 282: 5641-5652.
48. Yamamoto A, Lucas JJ, Hen R, (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101: 57-66.
49. Sah DW, Aronin N, (2011) Oligonucleotide therapeutic approaches for Huntington disease. J Clin Invest 121: 500-507.
50. Warrick JM, Morabito LM, Bilen J, Gordesky-Gold B, Faust LZ, et al. (2005) Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism. Mol Cell 18: 37-48.
51. Alves S, Nascimento-Ferreira I, Dufour N, Hassig R, Auregan G, et al. (2010) Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? Hum Mol Genet 19: 2380-2394.
52. Schmitt I, Linden M, Khazneh H, Evert BO, Breuer P, et al. (2007) Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination. Biochem Biophys Res Commun 362: 734-739.
53. Crespo-Barreto J, Fryer JD, Shaw CA, Orr HT, Zoghbi HY, (2010) Partial loss of ataxin-1 function contributes to transcriptional dysregulation in spinocerebellar ataxia type 1 pathogenesis. PLoS Genet 6: e1001021.
54. Shen Y, Lee G, Choe Y, Zoltewicz JS, Peterson AS, (2007) Functional architecture of atrophins. J Biol Chem 282: 5037-5044.
55. Zhang Y, Engelman J, Friedlander RM, (2009) Allele-specific silencing of mutant Huntington's disease gene. J Neurochem 108: 82-90.
56. Lombardi MS, Jaspers L, Spronkmans C, Gellera C, Taroni F, et al. (2009) A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference. Exp Neurol 217: 312-319.
57. Pfister EL, Kennington L, Straubhaar J, Wagh S, Liu WZ, et al. (2009) Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. Curr Biol 19: 774-778.
58. Fedorov Y, Anderson EM, Birmingham A, Reynolds A, Karpilow J, et al. (2006) Off-target effects by siRNA can induce toxic phenotype. RNA 12: 1188-1196.
59. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, et al. (2006) Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441: 537-541.
60. Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, et al. (2011) Systemic Administration of PRO051 in Duchenne's muscular dystrophy. New Engl J Med 364: 1513-1522.
61. van Deutekom JC, Janson AA, Ginjaar IB, Frankhuizen WS, Aartsma-Rus A, et al. (2007) Local dystrophin restoration with antisense oligonucleotide PRO051. New Engl J Med 357: 2677-2686.
62. Passini MA, Bu J, Richards AM, Kinnecom C, Sardi SP, et al. (2011) Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci Transl Med 3: 72ra18.
63. Mulders SAM, van den Broek WJAA, Wheeler TM, Croes HJE, Kuik-Romeijn P, et al. (2009) Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy. P Natl Acad Sci USA 106: 13915-13920.
64. de Mezer M, Wojciechowska M, Napierala M, Sobczak K, Krzyzosiak WJ, (2011) Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference. Nucleic Acids Res 39: 3852-3863.
65. Aartsma-Rus A, Bremmer-Bout M, Janson AAM, den Dunnen JT, van Ommen GJB, et al. (2002) Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Neuromuscular Disord 12: S71-S77.
66. Pfaffl MW, (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.
67. Ruijter JM, Ramakers C, Hoogaars WMH, Karlen Y, Bakker O, et al. (2009) Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 37: e45.