Skipping multiple exons of dystrophin transcripts using cocktail antisense oligonucleotides

Nucleic Acid Therapeutics

Volumn 24, Issue 1, 2014, Pages 57-68

  Echigoya, Yusuke ^a   Yokota, Toshifumi ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DRISAPERSEN; DYSTROPHIN; MESSENGER RNA; MORPHOLINO OLIGONUCLEOTIDE; TOLL LIKE RECEPTOR;

CANINE MODEL; DUCHENNE MUSCULAR DYSTROPHY; EXON SKIPPING; GENE DELETION; GENE DUPLICATION; GENE MUTATION; GENE STRUCTURE; GENETIC TRANSCRIPTION; HUMAN; MULTIPLE EXON SKIPPING THERAPY; NONHUMAN; NONSENSE MUTATION; PRIORITY JOURNAL; REVIEW;

ANIMALS; DOG DISEASES; DOGS; DYSTROPHIN; EXONS; HUMANS; MALE; MICE; MICE, INBRED MDX; MUSCULAR DYSTROPHY, ANIMAL; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION; OLIGONUCLEOTIDES, ANTISENSE; RNA SPLICING; TARGETED GENE REPAIR;

EID: 84893553081     PISSN: 21593337     EISSN: None     Source Type: Journal    
DOI: 10.1089/nat.2013.0451     Document Type: Review

References (122)

1. AARTSMA-RUS, A. (2012). Overview on AON design.Methods Mol. Biol. 867, 117-129.
2. AARTSMA-RUS, A., FOKKEMA, I., VERSCHUUREN, J., GINJAAR I., VAN DEUTEKOM, J., VAN OMMEN, G.J., and DEN DUNNEN, J.T. (2009). Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum. Mutat. 30, 293-299.
3. AARTSMA-RUS, A., JANSON, A.A., KAMAN, W.E., BREMMER-BOUT, M., VAN OMMEN, G.J., DEN DUNNEN, J.T., and VAN DEUTEKOM, J.C. (2004a). Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Am. J. Hum. Genet. 74, 83-92.
4. AARTSMA-RUS, A., JANSON, A.A., VAN OMMEN, G.J., and VAN DEUTEKOM, J.C. (2007). Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy. BMC Med. Genet. 8, 43.
5. AARTSMA-RUS, A., KAMAN, W.E., BREMMER-BOUT, M., JANSON, A.A., JANSON, A.A., DEN DUNNEN, J.T., VAN OMMEN, G.J., and VAN DEUTEKOM, J.C. (2004b). Comparative analysis of antisense oligonucleotide analogs for targeted DMD exon 46 skipping in muscle cells. Gene Ther. 11, 1391-1398.
6. AARTSMA-RUS, A., KAMAN, W.E., WEIJ, R., DEN DUNNEN, J.T., VAN OMMEN, G.J., and VAN DEUTEKOM, J.C.. (2006a). Exploring the frontiers of therapeutic exon skipping for Duchenne muscular dystrophy by double targeting within one or multiple exons. Mol. Ther. 14, 401-407.
7. AARTSMA-RUS, A., VAN DEUTEKOM, J.C., FOKKEMA, I.F., VAN OMMEN, G.J., and DEN DUNNEN, J.T. (2006b). 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, 135-44.
8. ADAMS, A.M., HARDING, P.L., IVERSEN, P.L., COLEMAN, C., FLETCHER, S., and WILTON, S.D. (2007). Antisense oligonucleotide induced exon skipping and the dystrophin gene transcript: cocktails and chemistries. BMC Mol. Biol. 8, 57.
9. ADKIN, C.F., MELONI, P.L., FLETCHER, S., ADAMS, A.M., MUNTONI, F., WONG, B., and WILTON, S.D. (2012). Multiple exon skipping strategies to by-pass dystrophin mutations. Neuromuscul. Disord. 22, 297-305.
10. ALTER, J., LOU, F., RABINOWITZ, A., YIN, H., ROSENFELD, J., WILTON, S.D., PARTRIDGE, T.A., and LU, Q.L. (2006). Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat. Med. 12, 175-177.
11. AMANTANA, A., MOULTON, H.M., CATE, M.L., REDDY, M.T., WHITEHEAD, T., HASSINGER, J.N., YOUNGBLOOD, D.S., and IVERSEN, P.L. (2007). Pharmacokinetics, biodistribution, stability and toxicity of a cell-penetrating peptide-morpholino oligomer conjugate. Bioconjug. Chem. 18, 1325-1331.
12. AOKI, Y., YOKOTA, T., NAGATA, T., NAKAMURA, A., TANIHATA, J., SAITO, T., DUGUEZ, S.M., NAGARAJU, K., HOFFMAN, E.P., PARTRIDGE, T., and TAKEDA, S. (2012). Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense delivery. Proc. Natl. Acad. Sci. U.S.A. 109, 13763-13768.
13. AOKI, Y., YOKOTA, T., and WOOD, M.J. (2013). Development of multiexon skipping antisense oligonucleotide therapy for duchenne muscular dystrophy. Biomed. Res. Int. 2013, 402369.
14. BANKS, G.B., JUDGE, L.M., ALLEN, J.M., and CHAMBERLAIN, J.S. (2010). The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins. PLoS Genet. 6, e1000958.
15. BARBUJANI, G., RUSSO, A., DANIELI, G.A., SPIEGLER, A.W., BORKOWSKA, J., and PETRUSEWICZ, I.H. (1990). Segregation analysis of 1885 DMD families: significant departure from the expected proportion of sporadic cases. Hum. Genet. 84, 522-526.
16. BÉROUD, C., TUFFERY-GIRAUD, S., MATSUO, M., HAMROUN, D., HUMBERTCLAUDE, V., MONNIER, N., MOIZARD, M.P., VOELCKEL, M.A., CALEMARD, L.M., BOISSEAU, P., et al. (2007). Multiexon skipping leading to an artificial 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.
17. BETTS, C., SALEH, A.F., ARZUMANOV, A.A., HAMMOND, S.M., GODFREY, C., COURSINDEL, T., GAIT, M.J., and WOOD, M.J. (2012). Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment. Mol. Ther. Nucleic Acids 1, e38.
18. BIES, R.D., CASKEY, C.T., and FENWICK, R. (1992). An intact cysteine-rich domain is required for dystrophin function. J. Clin. Invest. 90, 666-672.
19. BRETAG, A.H. (2007). Stem cell treatment of dystrophic dogs. Nature 450, E23; discussion E23-25.
20. CASKEY, C.T., NUSSBAUM, R.L., COHAN, L.C., and POLLACK, L. (1980). Sporadic occurrence of Duchenne muscular dystrophy: evidence for new mutation. Clin. Genet. 18, 329-341.
21. CHAMBERLAIN, J.S., GRANT, S.G., REEVES, A.A., MULLINS, L.J., STEPHENSON, D.A., HOFFMAN, E.P., MONACO, A.P., KUNKEL, L.M., CASKEY, C.T., and CHAPMAN, V.M. (1987). Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome. Somat. Cell Mol. Genet. 13, 671-678.
22. CHAPMAN, V.M., MILLER, D.R., ARMSTRONG, D., and CASKEY, C.T. (1989). Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc. Natl. Acad. Sci. U.S.A. 86, 1292-1296.
23. CIRAK, S., ARECHAVALA-GOMEZA, V., GUGLIERI, M., FENG, L., TORELLI, S., ANTHONY, K., ABBS, S., GARRALDA, M.E., BOURKE, J., and WELLS, D.J. (2011). Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, doseescalation study. Lancet 378, 595-605.
24. CIRAK, S., FENG, L., ANTHONY, K., ARECHAVALAGOMEZA, V., TORELLI, S., SEWRY, C., MORGAN, J.E., and MUNTONI, F. (2012). Restoration of the dystrophinassociated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy. Mol. Ther. 20, 462-467.
25. DANKO, I., CHAPMAN, V., and WOLFF, J.A. (1992). The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. Pediatr. Res. 32, 128-131.
26. DENT, K.M., DUNN, D.M., VON NIEDERHAUSERN, A.C., AOYAGI, A.T., KERR, L., BROMBERG, M.B., HART, K.J., TUOHY, T., WHITE, S., DEN DUNNEN, J.T., et al. (2005). Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am. J. Med. Genet. A 134, 295-298.
27. DUCHENNE. (1867). The pathology of paralysis with muscular degeneration (paralysie myosclerotique), or paralysis with apparent hypertrophy. Br. Med. J. 2, 541-542.
28. EAGLE, M., BAUDOUIN, S.V., CHANDLER, C., GIDDINGS, D.R., BULLOCK, R., and BUSHBY, K.. (2002). Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul. Disord. 12, 926-929.
29. ENGLAND, S.B., NICHOLSON, L.V., JOHNSON, M.A., FORREST, S.M., LOVE, D.R., ZUBRZYCKA-GAARN, E.E., BULMAN, D.E., HARRIS, J.B., and DAVIES, K.E. (1990). Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 343, 180-182.
30. FALL, A.M., JOHNSEN, R., HONEYMAN, K., IVERSEN, P., FLETCHER, S., and WILTON, S.D. (2006). Induction of revertant fibres in the mdx mouse using antisense oligonucleotides. Genet. Vaccines Ther. 4, 3.
31. FINSTERER, J., and STOLLBERGER, C. (2001). Spontaneous left ventricular hypertrabeculation in dystrophin duplication based Becker's muscular dystrophy. Herz. 26, 477-481.
32. FINSTERER, J., and STOLLBERGER, C. (2003). The heart in human dystrophinopathies. Cardiology 99, 1-19.
33. FINSTERER, J., and STOLLBERGER, C. (2007). Cardiac involvement determines the prognosis of Duchenne muscular dystrophy. Indian J. Pediatr. 74, 209; author reply 210-212.
34. FLETCHER, S., HONEYMAN, K., FALL, A.M., HARDING, P.L., (2007). Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Mol. Ther. 15, 1587-1592.
35. FLETCHER, S., HONEYMAN, K., FALL, A.M., HARDING, P.L., JOHNSEN, R.D., STEINHAUS, J.P., MOULTON, H.M., IVERSEN, P.L., and WILTON, S.D. (2006). Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide. J. Gene Med. 8, 207-216.
36. FORREST, S., MELONI, P.L., MUNTONI, F., KIM, J., FLETCHER, S., and WILTON, S.D. (2010). Personalized exon skipping strategies to address clustered non-deletion dystrophin mutations. Neuromuscul. Disord. 20, 810-816.
37. GEBSKI, B.L., MANN, C.J., FLETCHER, S., and WILTON, S.D. (2003). Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle. Hum. Mol. Genet. 12, 1801-1811.
38. GOEMANS, N.M., TULINIUS, M., VAN DEN AKKER, J.T., BURM, B.E., EKHART, P.F., HEUVELMANS, N., HOLLING, T., JANSON, A.A., PLATENBURG, G.J., SIPKENS, J.A., SITSEN, J.M., AARTSMA-RUS, A., VAN OMMEN, G.J., BUYSE, G., et al. (2011). Systemic administration of PRO051 in Duchenne's muscular dystrophy. N. Engl. J. Med. 364, 1513-1522.
39. GOYENVALLE, A., BABBS, A., POWELL, D., KOLE, R., FLETCHER, S., WILTON, S.D., and DAVIES, K.E. (2010). Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomermediated exon-skipping. Mol. Ther. 18, 198-205.
40. HARDING, P.L., FALL, A.M., HONEYMAN, K., FLETCHER, S., and WILTON, S.D. (2007). The influence of antisense oligonucleotide length on dystrophin exon skipping. Mol. Ther. 1, 157-166.
41. HARPER, S.Q., HAUSER, M.A., DELLORUSSO, C., DUAN, D., CRAWFORD, R.W., PHELPS, S.F., HARPER, H.A., ROBINSON, A.S., ENGELHARDT, J.F., BROOKS, S.V., and CHAMBERLAIN, J.S. (2002). Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat. Med. 8, 253-261.
42. HEEMSKERK, H., DE WINTER, C., VAN KUIK, P., HEUVELMANS, N., SABATELLI, P., RIMESSI, P., BRAGHETTA, P., VAN OMMEN, G.J., DE KIMPE, S., FERLINI, A., et al. (2010). Preclinical PK and PD studies on 2'-Omethyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol. Ther. 18, 1210-1217.
43. HEEMSKERK, H., DE WINTER, C.L., VAN OMMEN, G.J., VAN DEUTEKOM, J.C., and AARTSMA-RUS, A. (2009a). Development of antisense-mediated exon skipping as a treatment for duchenne muscular dystrophy. Ann. N.Y. Acad. Sci. 1175, 71-79.
44. HEEMSKERK, H.A., DE WINTER, C.L., DE KIMPE, S.J., VAN KUIK-ROMEIJN, P., HEUVELMANS, N., PLATENBURG, G.J., VAN OMMEN, G.J., VAN DEUTEKOM, J.C., and AARTSMA-RUS, A. (2009b). In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J. Gene Med. 11, 257-266.
45. HOFFMAN, E.P., BROWN, R.H., JR., and KUNKEL, L.M. (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51, 919-928.
46. HUDZIAK, R.M., BAROFSKY, E., BAROFSKY, D.F., and WELLER, D.L. (1996). Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation. Antisense Nucleic Acid Drug Dev. 6, 267-272.
47. JÄ RVER, P., O'DONOVAN, L., and GAIT, M.J. (2013). A chemical view of oligonucleotides for exon skipping and related drug applications. Nucleic Acid Ther., [Epub ahead of press]; DOI:10.1089/nat.2013.0454.
48. JEARAWIRIYAPAISARN, N., MOULTON, H.M., BUCKLEY, B., ROBERTS, J., SAZANI, P., FUCHAROEN, S., IVERSEN, P.L., and KOLE, R. (2008). Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Mol. Ther. 16, 1624-1629.
49. JEARAWIRIYAPAISARN, N., MOULTON, H.M., SAZANI, P., KOLE, R., and WILLIS, M.S. (2010). Long-term improvement in mdx cardiomyopathy after therapy with peptide-conjugated morpholino oligomers. Cardiovasc. Res. 85, 444-453.
50. JULIANO, R.L., MING, X., and NAKAGAWA, O. (2012). The chemistry and biology of oligonucleotide conjugates. Acc. Chem. Res. 45, 1067-1076.
51. KARKARE, S., and BHATNAGAR, D. (2006). Promising nucleic acid analogs and mimics: characteristic features and applications of PNA, LNA, and morpholino. Appl. Microbiol. Biotechnol. 71, 575-586.
52. KARPATI, G., and ACSADI, G. (1993). The potential for gene therapy in Duchenne muscular dystrophy and other genetic muscle diseases. Muscle Nerve 16, 1141-1153.
53. KINALI, M., ARECHAVALA-GOMEZA, V., FENG, L., CIRAK, S., HUNT, D., ADKIN, C., GUGLIERI, M., ASHTON, E., ABBS, S., NIHOYANNOPOULOS, P., et al. (2009). Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 8, 918-928.
54. KOENIG, M., HOFFMAN, E.P., BERTELSON, C.J., MONACO, A.P., FEENER, C., and KUNKEL, L.M.. (1987). Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50, 509-517.
55. KOO, T., MALERBA, A., ATHANASOPOULOS, T., TROLLET, C., BOLDRIN, L., FERRY, A., POPPLEWELL, L., FOSTER, H., FOSTER, K., and DICKSON, G. (2011). Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of alpha1-syntrophin and alpha-dystrobrevin in skeletal muscles of mdx mice. Hum. Gene Ther. 22, 1379-1388.
56. KORNEGAY, J.N., TULER, S.M., MILLER, D.M., and LEVESQUE, D.C. (1988). Muscular dystrophy in a litter of golden retriever dogs. Muscle Nerve 11, 1056-1064.
57. LAI, Y., THOMAS, G.D., YUE, Y., YANG, H.T., (2009). Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J. Clin. Invest. 119, 624-635.
58. LEE, J., and YOKOTA, T. (2013). Antisense therapy in neurology. J. Pers. Med. 3, 144-176.
59. MAGRI, F., GOVONI, A., D'ANGELO, M.G., DEL BO, R., GHEZZI, S., SANDRA, G., TURCONI, A.C., SCIACCO, M., CISCATO, P., BORDONI, A., et al. (2011). Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up. J. Neurol. 258, 1610-1623.
60. MALERBA, A., BOLDRIN, L., and DICKSON, G. (2011). Long-term systemic administration of unconjugated morpholino oligomers for therapeutic expression of dystrophin by exon skipping in skeletal muscle: implications for cardiac muscle integrity. Nucleic Acid Ther. 21, 293-298.
61. MALERBA, A., THOROGOOD, F.C., DICKSON, G., and GRAHAM, I.R. (2009). Dosing regimen has a significant impact on the efficiency of morpholino oligomer-induced exon skipping in mdx mice. Hum. Gene Ther. 20, 955-965.
62. MALIK, V., RODINO-KLAPAC, L.R., VIOLLET, L., and MENDELL, J.R. (2010). Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. Ther. Adv. Neurol. Disord. 3, 379-389.
63. MCCLOREY, G., MOULTON, H.M., IVERSEN, P.L., FLETCHER, S., and WILTON, S.D. (2006a). Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther. 13, 1373-1381.
64. MCCLOREY, G., FALL, A.M., MOULTON, H.M., IVERSEN, P.L., RASKO, J.E., RYAN, M., FLETCHER, S., and WILTON, S.D. (2006b). Induced dystrophin exon skipping in human muscle explants. Neuromuscul. Disord. 16, 583-590.
65. MITRPANT, C., FLETCHER, S., IVERSEN, P.L., and WILTON, S.D. (2009). By-passing the nonsense mutation in the 4 CV mouse model of muscular dystrophy by induced exon skipping. J. Gene Med. 11, 46-56.
66. MIYAZATO, L.G., MORAES, J.R., BERETTA, D.C., and KORNEGAY, J.N. (2011). Muscular dystrophy in dogs: does the crossing of breeds influence disease phenotype? Vet. Pathol. 48, 655-662.
67. MOONEY, D.J., and VANDENBURGH, H. (2008). Cell delivery mechanisms for tissue repair. Cell Stem Cell 2, 205-213.
68. MORCOS, P.A., LI, Y., and JIANG, S. (2008). Vivo-morpholinos: a non-peptide transporter delivers morpholinos into a wide array of mouse tissues. Biotechniques 45, 613-614, 616, 618 passim.
69. MOULTON, H.M. (2012). Cell-penetrating peptides enhance systemic delivery of antisense morpholino oligomers. Methods Mol. Biol. 867, 407-414.
70. MOULTON, H.M., and MOULTON, J.D. (2010). Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim. Biophys. Acta 1798, 2296-2303.
71. NAKAMURA, A., and TAKEDA, S. (2011). Mammalian models of Duchenne muscular dystrophy: pathological characteristics and therapeutic applications. J. Biomed. Biotechnol. 2011, 184393.
72. NAKAMURA, A., YOSHIDA, K., FUKUSHIMA, K., UEDA, H., URASAWA, N., KOYAMA, J., YAZAKI, Y., YAZAKI, M., SAKAI, T., HARUTA, S., et al. (2008). Follow-up of three patients with a large in-frame deletion of exons 45-55 in the Duchenne muscular dystrophy (DMD) gene. J. Clin. Neurosci. 15, 757-763.
73. NGUYEN, F., CHEREL, Y., GUIGAND, L., GOUBAULTLEROUX, I., and WYERS, M. (2002). Muscle lesions associated with dystrophin deficiency in neonatal golden retriever puppies. J. Comp. Pathol. 126, 100-108.
74. NISHIDA, M., BABA, T., KODAMA, T., YAHARA, A., IMANISHI, T., and OBIKA, S. (2010). Synthesis, RNA selective hybridization and high nuclease resistance of an oligonucleotide containing novel bridged nucleic acid with cyclic urea structure. Chem. Commun. (Camb.) 46, 5283-5285.
75. NOMURA, H., and HIZAWA, K. (1982). Histopathological study of the conduction system of the heart in Duchenne progressive muscular dystrophy. Acta Pathol. Jpn. 32, 1027-1033.
76. OHSHIMA, S., SHIN, J.H., YUASA, K., NISHIYAMA, A., KIRA, J., OKADA, T., and TAKEDA, S. (2009). Transduction efficiency and immune response associated with the administration of AAV8 vector into dog skeletal muscle. Mol. Ther. 17, 73-80.
77. PASSAMANO, L., TAGLIA, A., PALLADINO, A., VIGGIANO, E., D'AMBROSIO, P., SCUTIFERO, M., ROSARIA CECIO, M., TORRE, V., DE LUCA, F., PICILLO, E., et al. (2012). Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients. Acta Myol. 31, 121-125.
78. POPPLEWELL, L.J., TROLLET, C., DICKSON, G., and GRAHAM, I.R. (2009). Design of phosphorodiamidate morpholino oligomers (PMOs) for the induction of exon skipping of the human DMD gene. Mol. Ther. 17, 554-561.
79. QUENNEVILLE, S.P., CHAPDELAINE, P., SKUK, D., PARADIS, M., GOULET, M., ROUSSEAU, J., XIAO, X., GARCIA, L., TREMBLAY, J.P., et al. (2007). Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models. Mol. Ther. 15, 431-438.
80. ROBERTS, M.L., WELLS, D.J., GRAHAM, I.R., FABB, S.A., HILL, V.J., DUISIT, G., YUASA, K., TAKEDA, S., COSSET, F.L., and DICKSON, G. (2002). Stable micro-dystrophin gene transfer using an integrating adeno-retroviral hybrid vector ameliorates the dystrophic pathology in mdx mouse muscle. Hum. Mol. Genet. 11, 1719-1730.
81. RYBAKOVA, I.N., PATEL, J.R., and ERVASTI, J.M. (2000). The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J. Cell Biol. 150, 1209-1214.
82. SAITO, T., NAKAMURA, A., AOKI, Y., YOKOTA, T., OKADA, T., OSAWA, M., and TAKEDA, S. (2010). Antisense PMO found in dystrophic dog model was effective in cells from exon 7-deleted DMD patient. PLoS One 5, e12239.
83. SAKAMOTO, M., YUASA, K., YOSHIMURA, M., YOKOTA, T., IKEMOTO, T., SUZUKI, M., DICKSON, G., MIYAGOESUZUKI, Y., and TAKEDA, S. (2002). Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx mice as a transgene. Biochem. Biophys. Res. Commun. 293, 1265-1272.
84. SAZANI, P., NESS, K.P., WELLER, D.L., POAGE, D., NELSON, K., and SHREWSBURY, A.S. (2011). Chemical and mechanistic toxicology evaluation of exon skipping phosphorodiamidate morpholino oligomers in mdx mice. Int. J. Toxicol. 30, 322-333.
85. SEIO, K., MIYAZAKI, K., KUROHAGI, S., MASAKI, Y., TSUNODA, H., OHKUBO, A., and SEKINE, M. (2009). Synthesis and properties of terminally modified oligonucleotides capable of short-RNA selective hybridization. Nucleic Acids Symp. Ser. (Oxf.) 2009, 13-14.
86. SHARP, N.J., KORNEGAY, J.N., VAN CAMP, S.D., HERBSTREITH, M.H., SECORE, S.L., KETTLE, S., HUNG, W.Y., CONSTANTINOU, C.D., DYKSTRA, M.J., ROSES, A.D., 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.
87. SHIMATSU, Y., KATAGIRI, K., FURUTA, T., NAKURA, M., TANIOKA, Y., YUASA, K., TOMOHIRO, M., KORNEGAY, J.N., NONAKA, I., and TAKEDA, S. (2003). Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp. Anim. 52, 93-97.
88. SHIMATSU, Y., YOSHIMURA, M., YUASA, K., URASAWA, N., TOMOHIRO, M., NAKURA, M., TANIGAWA, M., NAKAMURA, A., and TAKEDA, S. (2005). Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMDJ. Acta Myol. 24, 145-154.
89. SHIN, J.H., YUE, Y., SRIVASTAVA, A., SMITH, B., LAI, Y., and DUAN, D. (2012). A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs. Hum. Gene Ther. 23, 202-209.
90. STOLLBERGER, C., and FINSTERER, J. (2005). Worsening of heart failure in Becker muscular dystrophy after nonsteroidal anti-inflammatory drugs. South Med. J. 98, 478-480.
91. SUMMERTON, J.E. (2007). Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity. Curr. Top. Med. Chem. 7, 651-660.
92. SUMMERTON, J., and WELLER, D. (1997). Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 7, 187-195.
93. TAKESHIMA, Y., YAGI, M., OKIZUKA, Y., AWANO, H., ZHANG, Z., YAMAUCHI, Y., NISHIO, H., and MATSUO, M. (2010). Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J. Hum. Genet. 55, 379-388.
94. URASAWA, N., WADA, M.R., MACHIDA, N., YUASA, K., SHIMATSU, Y., WAKAO, Y., YUASA, S., SANO, T., NONAKA, I., NAKAMURA, A., and TAKEDA, S. (2008). Selective vacuolar degeneration in dystrophin-deficient canine Purkinje fibers despite preservation of dystrophin-associated proteins with overexpression of Dp71. Circulation 117, 2437-2448.
95. VAN DEUTEKOM, J.C., BREMMER-BOUT, M., JANSON, A.A., GINJAAR, I.B., BAAS, F., DEN DUNNEN, J.T., and VAN OMMEN, G.J. (2001). Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum. Mol. Genet. 10, 1547-1554.
96. VAN DEUTEKOM, J.C., JANSON, A.A., GINJAAR, I.B., FRANKHUIZEN, W.S., AARTSMA-RUS, A., BREMMERBOUT, M., DEN DUNNEN, J.T., KOOP, K., VAN DER KOOI, A.J.,GOEMANS, N.M., et al. (2007). Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 357, 2677-2686.
97. VAN VLIET, L., D.E., WINTER, C.L., VAN DEUTEKOM, J.C., VAN OMMEN, G.J., and AARTSMA-RUS, A. (2008). Assessment of the feasibility of exon 45-55 multiexon skipping for Duchenne muscular dystrophy. BMC Med. Genet. 9, 105.
98. WATKINS, S.C., CULLEN, M.J., HOFFMAN, E.P., and BILLINGTON, L. (2000). Plasma membrane cytoskeleton of muscle: a fine structural analysis. Microsc. Res. Tech. 48, 131-141.
99. WHITE, S.J., AARTSMA-RUS, A., FLANIGAN, K.M., WEISS, R.B., KNEPPERS, A.L., LALIC, T., JANSON, A.A., GINJAAR, H.B., BREUNING, M.H., and DEN DUNNEN, J.T. (2006). Duplications in the DMD gene. Hum. Mutat. 27, 938-945.
100. WILTON, S.D., FALL, A.M., HARDING, P.L., MCCLOREY, G., COLEMAN, C., and FLETCHER, S. (2007). Antisense oligonucleotide-induced exon skipping across the human dystrophin gene transcript. Mol. Ther. 15, 1288-1296.
101. WILTON, S.D., and FLETCHER, S. (2011). RNA splicing manipulation: strategies to modify gene expression for a variety of therapeutic outcomes. Curr. Gene Ther. 11, 259-275.
102. WU, B., BENRASHID, E., LU, P., CLOER, C., ZILLMER, A., SHABAN, M., and LU, Q.L. (2011a). Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development. PLoS One 6, e19906.
103. WU, B., LI, Y., MORCOS, PA., DORAN, T.J., LU, P., and LU, Q.L. (2009). Octa-guanidine morpholino restores dystrophin expression in cardiac and skeletal muscles and ameliorates pathology in dystrophic mdx mice. Mol. Ther. 17, 864-871.
104. WU, B., LU, P., BENRASHID, E., MALIK, S., ASHAR, J., DORAN, T.J., and LU, Q.L. (2010). Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino. Gene Ther. 17, 132-140.
105. WU, B., LU, P., CLOER, C., SHABAN, M., GREWAL, S., MILAZI, S., SHAH, S.N., MOULTON, H.M., and LU, Q.L. (2012). Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino. Am. J. Pathol. 181, 392-400.
106. WU, B., XIAO, B., CLOER, C., SHABAN, M., SALI, A., LU, P., LI, J., NAGARAJU, K., XIAO, X., and LU, Q.L. (2011b). One-year treatment of morpholino antisense oligomer improves skeletal and cardiac muscle functions in dystrophic mdx mice. Mol. Ther. 19, 576-583.
107. YIN, H., MOULTON, H., BETTS, C., and WOOD, M. (2011a). CPP-directed oligonucleotide exon skipping in animal models of Duchenne muscular dystrophy. Methods Mol. Biol. 683, 321-338.
108. YIN, H., MOULTON, H.M., BETTS, C., MERRITT, T., SEOW, Y., ASHRAF, S., WANG, Q., BOUTILIER, J., and WOOD, M.J. (2010). Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO. Mol. Ther. 18, 1822-1829.
109. YIN. H., MOULTON. H.M., BETTS, C., SEOW, Y., BOUTILIER, J., IVERSON, P.L., and WOOD, M.J. (2009). A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum. Mol. Genet. 18, 4405-4414.
110. YIN, H., MOULTON, H.M., SEOW, Y., BOYD, C., BOUTILIER, J., IVERSON, P., and WOOD, M.J. (2008). Cellpenetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Hum. Mol. Genet. 17, 3909-3918.
111. YIN, H., SALEH, A.F., BETTS, C., CAMELLITI, P., SEOW, Y., ASHRAF, S., ARZUMANOV, A., HAMMOND, S., MERRITT, T., GAIT, M.J., and WOOD, M.J. (2011b). Pip5 transduction peptides direct high efficiency oligonucleotidemediated dystrophin exon skipping in heart and phenotypic correction in mdx mice. Mol. Ther. 19, 1295-1303.
112. YOKOTA, T., DUDDY, W., ECHIGOYA, Y., and KOLSKI, H. (2012a). Exon skipping for nonsense mutations in Duchenne muscular dystrophy: too many mutations, too few patients? Expert Opin. Biol. Ther. 12, 1141-1152.
113. YOKOTA, T., DUDDY, W., and PARTRIDGE, T. (2007a). Optimizing exon skipping therapies for DMD. Acta Myol. 26, 179-184.
114. YOKOTA, T., HOFFMAN, E., and TAKEDA, S. (2011). Antisense oligo-mediated multiple exon skipping in a dog model of Duchenne muscular dystrophy. Methods Mol. Biol. 709, 299-312.
115. YOKOTA, T., LU, Q.L., PARTRIDGE, T., KOBAYASHI, M., NAKAMURA, A., TAKEDA, S., and HOFFMAN, E. (2009a). Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann. Neurol. 65, 667-676.
116. YOKOTA, T., NAKAMURA, A., NAGATA, T., SAITO, T., KOBAYASHI, M., AOKI, Y., ECHIGOYA, Y., PARTRIDGE, T., HOFFMAN, E.P., and TAKEDA, S. (2012b). Extensive and prolonged restoration of dystrophin expression with vivo-morpholino-mediated multiple exon skipping in dystrophic dogs. Nucleic Acid Ther. 22, 306-315.
117. YOKOTA, T., PISTILLI, E., DUDDY, W., and NAGARAJU, K. (2007b). Potential of oligonucleotide-mediated exonskipping therapy for Duchenne muscular dystrophy. Expert Opin. Biol. Ther. 7, 831-842.
118. YOKOTA, T., TAKEDA, S., LU, Q.L., PARTRIDGE, T.A., NAKAMURA, A., and HOFFMAN, E.P. (2009b). A renaissance for antisense oligonucleotide drugs in neurology: exon skipping breaks new ground. Arch. Neurol. 66, 32-38.
119. YOSHIMURA, M., SAKAMOTO, M., IKEMOTO, M., MOCHIZUKI, Y., YUASA, K., MIYAGOE-SUZUKI, Y., and TAKEDA, S. (2004). AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype. Mol. Ther. 10, 821-828.
120. YUASA, K., MIYAGOE, Y., YAMAMOTO, K., NABESHIMA, Y., DICKSON, G., and TAKEDA, S.. (1998). Effective restoration of dystrophin-associated proteins in vivo by adenovirus-mediated transfer of truncated dystrophin cDNAs. FEBS Lett. 425, 329-336.
121. YUGETA, N., URASAWA, N., FUJII, Y., YOSHIMURA, M., YUASA, K., WADA, M.R., NAKURA, M., SHIMATSU, Y., TOMOHIRO, M., TAKAHASHI, A., et al. (2006). Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies. BMC Cardiovasc. Disord. 6, 47.
122. ZELLWEGER, H., and ANTONIK, A. (1975). Newborn screening for Duchenne muscular dystrophy. Pediatrics 55, 30-34.