Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington's Disease

Molecular Therapy Nucleic Acids

Volumn 5, Issue , 2016, Pages e297-

  Miniarikova, Jana ^a,b   Zanella, Ilaria ^a   Huseinovic, Angelina ^a   van der Zon, Tom ^a   Hanemaaijer, Evelyn ^a   Martier, Raygene ^a,b   Koornneef, Annemart ^a   Southwell, Amber L ^c   Hayden, Michael R ^c   van Deventer, Sander J ^b   Petry, Harald ^a   Konstantinova, Pavlina ^a  

^a UNIQURE   (Netherlands)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

adeno associated virus; gene silencing; humanized HD mouse model; Huntington's disease; therapeutic microRNAs

Indexed keywords

ADENO ASSOCIATED VIRUS 5 VECTOR; ADENO ASSOCIATED VIRUS VECTOR; HUNTINGTIN; MICRORNA; MOLECULAR SCAFFOLD; UNCLASSIFIED DRUG; BETA TUBULIN; MICRORNA 1 2; MICRORNA 101 1; MICRORNA 122; MICRORNA 135B; MICRORNA 155; MICRORNA 16 1; MICRORNA 203A; MICRORNA 26A 1; MICRORNA 335; MICRORNA 451A;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; EMBEDDING; EXON; GENE CASSETTE; GENE EXPRESSION; GENE MUTATION; GENE SILENCING; GENE TARGETING; GENETIC LINKAGE; HETEROZYGOTE; HUNTINGTON CHOREA; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; VIRAL GENE THERAPY; 3' UNTRANSLATED REGION; 5' UNTRANSLATED REGION; ANIMAL TISSUE; BRAIN CORTEX; CAG REPEAT; CORPUS STRIATUM; DNA FLANKING REGION; DRUG EFFICACY; HEK293 CELL LINE; HUMAN; HUMAN CELL; MUTANT; NEXT GENERATION SEQUENCING; NONVIRAL GENE THERAPY; NUCLEIC ACID BASE SUBSTITUTION; VIRAL GENE DELIVERY SYSTEM; WILD TYPE;

EID: 85015189278     PISSN: None     EISSN: 21622531     Source Type: Journal    
DOI: 10.1038/mtna.2016.7     Document Type: Article

References (57)

1. 1 Ross, CA, Tabrizi, SJ, Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10 (2011), 83–98.
2. 2 Southwell, AL, Patterson, PH, Gene therapy in mouse models of huntington disease. Neuroscientist 17 (2011), 153–162.
3. 3 Kay, C, Skotte, NH, Southwell, AL, Hayden, MR, Personalized gene silencing therapeutics for Huntington disease. Clin Genet 86 (2014), 29–36.
4. 4 Boudreau, RL, Rodríguez-Lebrón, E, Davidson, BL, RNAi medicine for the brain: progresses and challenges. Hum Mol Genet 20:R1 (2011), R21–R27.
5. 5 Aronin, N, DiFiglia, M, Huntingtin-lowering strategies in Huntington's disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord 29 (2014), 1455–1461.
6. 6 Østergaard, ME, Southwell, AL, Kordasiewicz, H, Watt, AT, Skotte, NH, Doty, CN, et al. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res 41 (2013), 9634–9650.
7. 7 Southwell, AL, Skotte, NH, Kordasiewicz, HB, Østergaard, ME, Watt, AT, Carroll, JB, et al. In vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides. Mol Ther 22 (2014), 2093–2106.
8. 8 Stiles, DK, Zhang, Z, Ge, P, Nelson, B, Grondin, R, Ai, Y, et al. Widespread suppression of huntingtin with convection-enhanced delivery of siRNA. Exp Neurol 233 (2012), 463–471.
9. 9 Stanek, LM, Sardi, SP, Mastis, B, Richards, AR, Treleaven, CM, Taksir, T, et al. Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of Huntington's disease. Hum Gene Ther 25 (2014), 461–474.
10. 10 Drouet, V, Perrin, V, Hassig, R, Dufour, N, Auregan, G, Alves, S, et al. Sustained effects of nonallele-specific Huntingtin silencing. Ann Neurol 65 (2009), 276–285.
11. 11 Maczuga, P, Koornneef, A, Borel, F, Petry, H, van Deventer, S, Ritsema, T, et al. Optimization and comparison of knockdown efficacy between polymerase II expressed shRNA and artificial miRNA targeting luciferase and Apolipoprotein B100. BMC Biotechnol, 12, 2012, 42.
12. 12 Southwell, AL, Skotte, NH, Bennett, CF, Hayden, MR, Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases. Trends Mol Med 18 (2012), 634–643.
13. 13 McBride, JL, Pitzer, MR, Boudreau, RL, Dufour, B, Hobbs, T, Ojeda, SR, et al. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Mol Ther 19 (2011), 2152–2162.
14. 14 Grondin, R, Kaytor, MD, Ai, Y, Nelson, PT, Thakker, DR, Heisel, J, et al. Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum. Brain 135:Pt 4 (2012), 1197–1209.
15. 15 Yu, D, Pendergraff, H, Liu, J, Kordasiewicz, HB, Cleveland, DW, Swayze, EE, et al. Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 150 (2012), 895–908.
16. 16 Carroll, JB, Warby, SC, Southwell, AL, Doty, CN, Greenlee, S, Skotte, N, et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele-specific silencing of mutant huntingtin. Mol Ther 19 (2011), 2178–2185.
17. 17 Pfister, EL, Kennington, L, Straubhaar, J, Wagh, S, Liu, W, DiFiglia, M, et al. Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. Curr Biol 19 (2009), 774–778.
18. 18 Drouet, V, Ruiz, M, Zala, D, Feyeux, M, Auregan, G, Cambon, K, et al. Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells. PLoS One, 9, 2014, e99341.
19. 19 Monteys, AM, Wilson, MJ, Boudreau, RL, Spengler, RM, Davidson, BL, Artificial miRNAs targeting mutant Huntingtin show preferential silencing in vitro and in vivo. Mol Ther Nucleic Acids, 4, 2015, e234.
20. 20 Lombardi, MS, Jaspers, L, Spronkmans, C, Gellera, C, Taroni, F, Di Maria, E, et al. A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference. Exp Neurol 217 (2009), 312–319.
21. 21 Kremer, B, Goldberg, P, Andrew, SE, Theilmann, J, Telenius, H, Zeisler, J, Squitieri, F, et al. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 330 (1994), 1401–1406.
22. 22 Kay, C, Collins, JA, Skotte, NH, Southwell, AL, Warby, SC, Caron, NS, et al. Huntingtin haplotypes provide prioritized target panels for allele-specific silencing in Huntington disease patients of European Ancestry. Mol Ther 23 (2015), 1759–1771.
23. 23 Fiszer, A, Mykowska, A, Krzyzosiak, WJ, Inhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats. Nucleic Acids Res 39 (2011), 5578–5585.
24. 24 Evers, MM, Pepers, BA, van Deutekom, JC, Mulders, SA, den Dunnen, JT, Aartsma-Rus, A, et al. Targeting several CAG expansion diseases by a single antisense oligonucleotide. PLoS One, 6, 2011, e 24308.
25. 25 Gagnon, KT, Pendergraff, HM, Deleavey, GF, Swayze, EE, Potier, P, Randolph, J, et al. Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Biochemistry 49 (2010), 10166–10178.
26. 26 Ohnishi, Y, Tamura, Y, Yoshida, M, Tokunaga, K, Hohjoh, H, Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi. PLoS One, 3, 2008, e2248.
27. 27 Klein, RL, Hamby, ME, Gong, Y, Hirko, AC, Wang, S, Hughes, JA, et al. Dose and promoter effects of adeno-associated viral vector for green fluorescent protein expression in the rat brain. Exp Neurol 176 (2002), 66–74.
28. 28 Khvorova, A, Reynolds, A, Jayasena, SD, Functional siRNAs and miRNAs exhibit strand bias. Cell 115 (2003), 209–216.
29. 29 Meijer, HA, Smith, EM, Bushell, M, Regulation of miRNA strand selection: follow the leader?. Biochem Soc Trans 42 (2014), 1135–1140.
30. 30 Gu, S, Jin, L, Zhang, F, Huang, Y, Grimm, D, Rossi, JJ, et al. Thermodynamic stability of small hairpin RNAs highly influences the loading process of different mammalian Argonautes. Proc Natl Acad Sci USA 108 (2011), 9208–9213.
31. 31 Martí, E, Pantano, L, Bañez-Coronel, M, Llorens, F, Miñones-Moyano, E, Porta, S, et al. A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing. Nucleic Acids Res 38 (2010), 7219–7235.
32. 32 Aravin, A, Tuschl, T, Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett 579 (2005), 5830–5840.
33. 33 Landgraf, P, Rusu, M, Sheridan, R, Sewer, A, Iovino, N, Aravin, A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129 (2007), 1401–1414.
34. 34 DiFiglia, M, Sena-Esteves, M, Chase, K, Sapp, E, Pfister, E, Sass, M, et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci USA 104 (2007), 17204–17209.
35. 35 Kordasiewicz, HB, Stanek, LM, Wancewicz, EV, Mazur, C, McAlonis, MM, Pytel, KA, et al. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 74 (2012), 1031–1044.
36. 36 Borel, F, van Logtenstein, R, Koornneef, A, Maczuga, P, Ritsema, T, Petry, H, et al. In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs. J RNAi Gene Silencing 7 (2011), 434–442.
37. 37 Bish, LT, Sleeper, MM, Reynolds, C, Gazzara, J, Withnall, E, Singletary, GE, et al. Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines. Hum Gene Ther 22 (2011), 969–977.
38. 38 Grimm, D, Streetz, KL, Jopling, CL, Storm, TA, Pandey, K, Davis, CR, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441 (2006), 537–541.
39. 39 McBride, JL, Boudreau, RL, Harper, SQ, Staber, PD, Monteys, AM, Martins, I, et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc Natl Acad Sci USA 105 (2008), 5868–5873.
40. 40 Boudreau, RL, McBride, JL, Martins, I, Shen, S, Xing, Y, Carter, BJ, et al. Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol Ther 17 (2009), 1053–1063.
41. 41 Hu, J, Liu, J, Corey, DR, Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism. Chem Biol 17 (2010), 1183–1188.
42. 42 Lee, Y, Kim, M, Han, J, Yeom, KH, Lee, S, Baek, SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23 (2004), 4051–4060.
43. 43 Auyeung, VC, Ulitsky, I, McGeary, SE, Bartel, DP, Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing. Cell 152 (2013), 844–858.
44. 44 Gregory, RI, Yan, KP, Amuthan, G, Chendrimada, T, Doratotaj, B, Cooch, N, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 432 (2004), 235–240.
45. 45 Han, J, Lee, Y, Yeom, KH, Kim, YK, Jin, H, Kim, VN, The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18 (2004), 3016–3027.
46. 46 Gurtan, AM, Lu, V, Bhutkar, A, Sharp, PA, In vivo structure-function analysis of human Dicer reveals directional processing of precursor miRNAs. RNA 18 (2012), 1116–1122.
47. 47 Monteys, AM, Spengler, RM, Dufour, BD, Wilson, MS, Oakley, CK, Sowada, MJ, et al. Single nucleotide seed modification restores in vivo tolerability of a toxic artificial miRNA sequence in the mouse brain. Nucleic Acids Res 42 (2014), 13315–13327.
48. 48 Cheloufi, S, Dos Santos, CO, Chong, MM, Hannon, GJ, A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465 (2010), 584–589.
49. 49 Cifuentes, D, Xue, H, Taylor, DW, Patnode, H, Mishima, Y, Cheloufi, S, et al. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science 328 (2010), 1694–1698.
50. 50 Ma, H, Zhang, J, Wu, H, Designing Ago2-specific siRNA/shRNA to Avoid Competition with Endogenous miRNAs. Mol Ther Nucleic Acids, 3, 2014, e176.
51. 51 Herrera-Carrillo, E, Harwig, A, Liu, YP, Berkhout, B, Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity. RNA 20 (2014), 1410–1418.
52. 52 Yoda, M, Cifuentes, D, Izumi, N, Sakaguchi, Y, Suzuki, T, Giraldez, AJ, et al. Poly(A)-specific ribonuclease mediates 3'-end trimming of Argonaute2-cleaved precursor microRNAs. Cell Rep 5 (2013), 715–726.
53. 53 Lee, M, Kim, B, Kim, VN, Emerging roles of RNA modification: m(6)A and U-tail. Cell 158 (2014), 980–987.
54. 54 Ameres, SL, Zamore, PD, Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 14 (2013), 475–488.
55. 55 Ha, M, Kim, VN, Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15 (2014), 509–524.
56. 56 D'ambrogio, A, Gu, W, Udagawa, T, Mello, CC, Richter, JD, Specific miRNA stabilization by Gld2-catalyzed monoadenylation. Cell Rep 2 (2012), 1537–1545.
57. 57 Southwell, AL, Ko, J, Patterson, PH, Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. J Neurosci 29 (2009), 13589–13602.