Overview on DMD exon skipping

Methods in Molecular Biology

Volumn 867, Issue , 2012, Pages 97-116

  Aartsma Rus, Annemieke ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Antisense oligonucleotides; Duchenne muscular dystrophy; Dystrophin; Exon skipping; Therapeutic development

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DYSTROPHIN;

ANIMAL; DUCHENNE MUSCULAR DYSTROPHY; EXON; GENE THERAPY; GENETICS; HUMAN; METHODOLOGY; MUTATION; NUCLEOTIDE SEQUENCE; REVIEW;

ANIMALS; DYSTROPHIN; EXONS; GENE THERAPY; HUMANS; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION; OLIGONUCLEOTIDES, ANTISENSE; READING FRAMES;

EID: 84859867996     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-61779-767-5_7     Document Type: Review

References (85)

1. Aartsma-Rus A, van Ommen GJ (2007) Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. RNA 13:1609-1624 (Pubitemid 47481669)
2. van Ommen GJ, van Deutekom J, Aartsma-Rus A (2008) The therapeutic potential of antisense-mediated exon skipping. Curr Opin Mol Ther 10:140-149 (Pubitemid 351498876)
3. Aartsma-Rus A (2010) Antisense-mediated modulation of splicing: therapeutic implications for duchenne muscular dystrophy. RNA Biol 7(4):453-461
4. Emery AE (2002) The muscular dystrophies. Lancet 359:687-695 (Pubitemid 34203773)
5. Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919-928
6. Monaco AP, Bertelson CJ, Liechti-Gallati S et al (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2:90-95
7. Blake DJ, Weir A, Newey SE et al (2002) Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82:291-329 (Pubitemid 34654455)
8. Koenig M, Kunkel LM (1990) Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer fl exibility. J Biol Chem 265:4560-4566
9. Aartsma-Rus A, van Deutekom JC, Fokkema IF et al (2006) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 34:135-144 (Pubitemid 44167796)
10. Aartsma-Rus A, Kaman WE, Bremmer-Bout M et al (2004) Comparative analysis of antisense oligonucleotide analogs for tageted DMD exon 46 skipping in muscle cells. Gene Therapy 11:1391-1398 (Pubitemid 39263892)
11. De Clercq E, Eckstein F, Sternbach H et al (1969) Interferon induction by and ribonuclease sensitivity of thiophosphate-substituted polyribonucleotides. Antimicrob Agents Chemother (Bethesda) 9:187-191
12. Crooke ST (2000) Progress in antisense technology: the end of the beginning. Methods Enzymol 313:3-45 (Pubitemid 29506409)
13. Sproat BS, Lamond AI, Beijer B et al (1989) Highly efficient chemical synthesis of 2'-O-methyloligoribonucleotides and tetrabiotinylated derivatives; novel probes that are resistant to degradation by RNA or DNA specific nucleases. Nucleic Acids Res 17:3373-3386 (Pubitemid 19120439)
14. Summerton J, Weller D (1997) Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev 7:187-195 (Pubitemid 27323077)
15. Obika S, Nanbu D, Hari Y et al (1998) Stability and structural features of the duplexes containing nucleoside analogues with fixed N-type conformation, 2'-O,4'-C-methyleneribonucleosides. Tetrahedron Lett 39:5401-5404 (Pubitemid 28295121)
16. Larsen HJ, Bentin T, Nielsen PE (1999) Antisense properties of peptide nucleic acid. Biochim Biophys Acta 1489:159-166
17. Takeshima Y, Nishio H, Sakamoto H et al (1995) Modulation of in vitro splicing of the upstream intron by modifying an intra-exon sequence which is deleted from the dystrophin gene in dystrophin Kobe. J Clin Invest 95: 515-520
18. Matsuo M, Masumura T, Nishio H et al (1991) Exon skipping during splicing of dystrophin mRNA precursor due to an intraexon deletion in the dystrophin gene of Duchenne muscular dystrophy kobe. J Clin Invest 87:2127-2131
19. Takeshima Y, Wada H, Yagi M et al (2001) Oligonucleotides against a splicing enhancer sequence led to dystrophin production in muscle cells from a Duchenne muscular dystrophy patient. Brain Dev 23:788-790 (Pubitemid 33101867)
20. van Deutekom JC, Bremmer-Bout M, Janson AA et al (2001) Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum Mol Genet 10:1547-1554 (Pubitemid 32734306)
21. Wilton SD, Lloyd F, Carville K et al (1999) Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides. Neuromuscul Disord 9:330-338 (Pubitemid 29301716)
22. Aartsma-Rus A, Janson AA, Kaman WE et al (2003) Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Hum Mol Genet 12:907-914 (Pubitemid 36504033)
23. Aartsma-Rus A, Janson AA, Kaman WE et al (2004) Antisense-induced multiexon skipping for duchenne muscular dystrophy makes more sense. Am J Hum Genet 74:83-92 (Pubitemid 38085240)
24. Arechavala-Gomeza V, Graham IR, Popplewell LJ et al (2007) Comparative analysis of antisense oligonucleotide sequences for targeted skipping of exon 51 during dystrophin premRNA splicing in human muscle. Hum Gene Ther 18:798-810 (Pubitemid 47502846)
25. Spitali P, Rimessi P, Fabris M et al (2009) Exon skipping-mediated dystrophin reading frame restoration for small mutations. Hum Mutat 30:1527-1534
26. Aartsma-Rus A, Janson AA, van Ommen GJ et al (2007) Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy. BMC Med Genet 8:43
27. Gurvich OL, Tuohy TM, Howard MT et al (2008) DMD pseudoexon mutations: splicing efficiency, phenotype, and potential therapy. Ann Neurol 63:81-89 (Pubitemid 351240554)
28. Madden HR, Fletcher S, Davis MR et al (2008) Characterization of a complex Duchenne muscular dystrophy-causing dystrophin gene inversion and restoration of the reading frame by induced exon skipping. Hum Mutat 30:22-28
29. McClorey G, Moulton HM, Iversen PL et al (2006) Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther 13:1373-1381 (Pubitemid 44420632)
30. Aartsma-Rus A, Fokkema I, Verschuuren J et al (2009) Theoretic applicability of antisensemediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat 30:293-299
31. Beroud C, Tuffery-Giraud S, Matsuo M et al (2007) Multiexon skipping leading to an artifi-cial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. Hum Mutat 28:196-202 (Pubitemid 46233317)
32. van Vliet L, De Winter CL, van Deutekom JC et al (2008) Assessment of the feasibility of exon 45-55 multiexon skipping for duchenne muscular dystrophy. BMC Med Genet 9:105
33. Aartsma-Rus A, Kaman WE, Weij R et al (2006) Exploring the frontiers of therapeutic exon skipping for duchenne muscular dystrophy by double targeting within one or multiple exons. Mol Ther 14:401-407 (Pubitemid 44184959)
34. Tennyson CN, Klamut HJ, Worton RG (1995) The human dystrophin gene requires 16 hours to be transcribed and is cotranscriptionally spliced. Nat Genet 9:184-190
35. Gebski BL, Mann CJ, Fletcher S et al (2003) Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle. Hum Mol Genet 12:1801-1811 (Pubitemid 36944135)
36. Popplewell LJ, Trollet C, Dickson G et al (2009) Design of phosphorodiamidate morpholino oligomers (PMOs) for the induction of exon skipping of the human DMD gene. Mol Ther 17:554-561
37. Popplewell LJ, Adkin C, Arechavala-Gomeza V et al (2010) Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: implications for future clinical trials. Neuromuscul Disord 20: 102-110
38. Wang Q, Yin H, Camelliti P et al (2010) In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular dystrophy. J Gene Med 12:354-364
39. Spitali P, Heemskerk H, Vossen RH et al (2010) Accurate quantification of dystrophin mRNA and exon skipping levels in Duchenne muscular dystrophy. Lab Invest 90(9):1396-1402
40. Sicinski P, Geng Y, Ryder-Cook AS et al (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244:1578-1580 (Pubitemid 19189735)
41. Willmann R, Possekel S, Dubach-Powell J et al (2009) Mammalian animal models for Duchenne muscular dystrophy. Neuromuscul Disord 19:241-249
42. Deconinck AE, Rafael JA, Skinner JA et al (1997) Utrophin-dystrophin- deficient mice as a model for Duchenne muscular dystrophy. Cell 90:717-727 (Pubitemid 27357963)
43. Zhou L, Rafael-Fortney JA, Huang P et al (2008) Haploinsufficiency of utrophin gene worsens skeletal muscle infl ammation and fibrosis in mdx mice. J Neurol Sci 264:106-111 (Pubitemid 350186318)
44. van Putten M., Kumar D., Hulsker M., et al (2012) Comparison of skeletal muscle pathology and motor function of dystrophin and utrophin deficient mouse strains. Neuromuscul Disord
45. 't Hoen PA, de Meijer EJ, Boer JM et al (2007) Generation and characterization of transgenic mice with the full-length human DMD gene. J Biol Chem 283:5899-5907
46. Bremmer-Bout M, Aartsma-Rus A, de Meijer EJ et al (2004) Targeted exon skipping in transgenic hDMD mice: a model for direct preclinical screening of human-specific antisense oligonucleotides. Mol Ther 10:232-240 (Pubitemid 39117869)
47. Sharp NJ, Kornegay JN, Van Camp SD et al (1992) An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics 13:115-121
48. Yokota T, Lu QL, Partridge T et al (2009) Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann Neurol 65:667-676
49. Walmsley GL, Arechavala-Gomeza V, Fernandez-Fuente M et al (2010) A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping. PLoS One 5:e8647
50. Lu QL, Mann CJ, Lou F et al (2003) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med 8:1009-1014 (Pubitemid 37021780)
51. Mann CJ, Honeyman K, McClorey G et al (2002) Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy. J Gene Med 4: 644-654 (Pubitemid 40277188)
52. Heemskerk HA, De Winter CL, de Kimpe SJ et al (2009) In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J Gene Med 11: 257-266
53. Yin H, Lu Q, Wood M (2008) Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx mice. Mol Ther 16:38-45
54. Watanabe TA, Geary RS, Levin AA (2006) Plasma protein binding of an antisense oligonucleotide targeting human ICAM-1 (ISIS 2302). Oligonucleotides 16:169-180
55. Heemskerk H, de Winter C, van Kuik P et al (2010) Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol Ther 18(6):1210-1217
56. Amantana A, Iversen PL (2005) Pharmacokinetics and biodistribution of phosphorodiamidate morpholino antisense oligomers. Curr Opin Pharmacol 5:550-555 (Pubitemid 41258575)
57. Heemskerk H, De Winter CL, van Ommen GJ et al (2009) Development of antisense-mediated exon skipping as a treatment for duchenne muscular dystrophy. Ann N Y Acad Sci 1175: 71-79
58. Lu QL, Rabinowitz A, Chen YC et al (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in bodywide skeletal muscles. Proc Natl Acad Sci USA 102:198-203 (Pubitemid 40094452)
59. Ferlini A, Sabatelli P, Fabris M et al (2010) Dystrophin restoration in skeletal, heart and skin arrector pili smooth muscle of mdx mice by ZM2 NP-AON complexes. Gene Ther 17:432-438
60. Alter J, Lou F, Rabinowitz A et al (2006) Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat Med 12:175-177 (Pubitemid 43214742)
61. Fletcher S, Honeyman K, Fall AM et al (2006) Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide. J Gene Med 8:207-216 (Pubitemid 43250701)
62. Fletcher S, Honeyman K, Fall AM et al (2007) Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Mol Ther 15:1587-1592 (Pubitemid 47289001)
63. Malerba A, Thorogood FC, Dickson G et al (2009) Dosing regimen has a significant impact on the efficiency of morpholino oligomerinduced exon skipping in mdx mice. Hum Gene Ther 20:955-965
64. Wu B, Lu P, Benrashid E et al (2010) Dosedependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino. Gene Ther 17: 132-140
65. Jearawiriyapaisarn N, Moulton HM, Buckley B et al (2008) Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Mol Ther 16:1624-1629
66. Wu B, Moulton HM, Iversen PL et al (2008) Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci USA 105:14814-14819
67. Yin H, Moulton HM, Seow Y et al (2008) Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Hum Mol Genet 17:3909-3918 (Pubitemid 352762853)
68. Goyenvalle A, Babbs A, Powell D et al (2010) Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomer-mediated exon-skipping. Mol Ther 18:198-205
69. Moulton HM, Moulton JD (2010) Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim Biophys Acta 1798(12):2296-2303
70. De Angelis FG, Sthandier O, Berarducci B et al (2002) Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in Delta 48-50 DMD cells. Proc Natl Acad Sci USA 99:9456-9461 (Pubitemid 34764635)
71. Denti MA, Rosa A, D'Antona G et al (2006) Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model. Proc Natl Acad Sci USA 103:3758-3763 (Pubitemid 43376628)
72. Denti MA, Incitti T, Sthandier O et al (2008) Long-term benefit of adeno-associated virus/antisense-mediated exon skipping in dystrophic mice. Hum Gene Ther 19:601-608 (Pubitemid 351913531)
73. Goyenvalle A, Vulin A, Fougerousse F et al (2004) Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306:1796-1799 (Pubitemid 39601401)
74. Goyenvalle A, Babbs A, van Ommen GJ et al (2009) Enhanced exon-skipping induced by U7 snRNA carrying a splicing silencer sequence: promising tool for DMD therapy. Mol Ther 17:1234-1240
75. Incitti T, De Angelis FG, Cazzella V et al (2010) Exon skipping and duchenne muscular dystrophy therapy: selection of the most active U1 snRNA antisense able to induce dystrophin exon 51 skipping. Mol Ther 18(9):1675-1682
76. van Deutekom JC, Janson AA, Ginjaar IB et al (2007) Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med 357:2677-2686
77. Kinali M, Arechavala-Gomeza V, Feng L et al (2009) Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a singleblind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol 8:918-928
78. Takeshima Y, Yagi M, Wada H et al (2006) Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy. Pediatr Res 59:690-694 (Pubitemid 43740012)
79. Pramono ZA, Takeshima Y, Alimsardjono H et al (1996) Induction of exon skipping of the dystrophin transcript in lymphoblastoid cells by transfecting an antisense oligodeoxynucleotide complementary to an exon recognition sequence. Biochem Biophys Res Commun 226:445-449 (Pubitemid 26331921)
80. Goemans NM, Tulinius M, van den Akker JT et al (2011) Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med 364:1513-1522
81. Cirak S, Arechavala-Gomeza V, Guglieri M et al (2011) Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378: 595-605
82. Muntoni F (2010) The development of antisense oligonucleotide therapies for Duchenne muscular dystrophy: report on a TREAT-NMD workshop hosted by the European Medicines Agency (EMA), on September 25th 2009. Neuromuscul Disord 20:355-362
83. Alagaratnam S, Mertens BJ, Dalebout JC et al (2008) Serum protein profiling in mice: identification of Factor XIIIa as a potential biomarker for muscular dystrophy. Proteomics 8:1552-1563 (Pubitemid 351580202)
84. Nadarajah VD, van Putten M, Chaouch A et al (2011) Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in duchenne muscular dystrophy (DMD). Neuromuscul Disord 21(8): 569-578
85. Melis MA, Cau M, Muntoni F et al (1998) Elevation of serum creatine kinase as the only manifestation of an intragenic deletion of the dystrophin gene in three unrelated families. Eur J Paediatr Neurol 2:255-261 (Pubitemid 28553033)