Exon-skipping antisense oligonucleotides to correct missplicing in neurogenetic diseases

Nucleic Acid Therapeutics

Volumn 24, Issue 1, 2014, Pages 69-86

  Siva, Kavitha ^a   Covello, Giuseppina ^a   Denti, Michela A ^a,b  

^a UNIVERSITY OF TRENTO   (Italy)

^b CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; MESSENGER RNA PRECURSOR;

ALTERNATIVE RNA SPLICING; ATAXIA TELANGIECTASIA; CHROMOSOME 17; CONGENITAL DISORDER OF GLYCOSYLATION; EXON SKIPPING; FRONTOTEMPORAL DEMENTIA; GENE THERAPY; HUMAN; LEUKOENCEPHALOPATHY; MEGALENCEPHALIC LEUKOENCEPHALOPATHY; NERVOUS SYSTEM; NEUROFIBROMATOSIS; NEUROFIBROMATOSIS TYPE 1; NEUROFIBROMATOSIS TYPE 2; NIEMANN PICK DISEASE; NONHUMAN; OPEN READING FRAME; PELIZAEUS MERZBACHER DISEASE; POINT MUTATION; PRIORITY JOURNAL; REVIEW; SPLICING DEFECT;

ANIMALS; ATAXIA TELANGIECTASIA; BLOOD-BRAIN BARRIER; CONGENITAL DISORDERS OF GLYCOSYLATION; CYSTS; DRUG DELIVERY SYSTEMS; EXONS; FRONTOTEMPORAL DEMENTIA; GENETIC DISEASES, INBORN; HEREDITARY CENTRAL NERVOUS SYSTEM DEMYELINATING DISEASES; HUMANS; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION; NERVOUS SYSTEM DISEASES; NEUROFIBROMATOSES; NIEMANN-PICK DISEASE, TYPE C; OLIGONUCLEOTIDES, ANTISENSE; PELIZAEUS-MERZBACHER DISEASE; PHOSPHOTRANSFERASES (PHOSPHOMUTASES); RNA SPLICING; TARGETED GENE REPAIR;

EID: 84893582109     PISSN: 21593337     EISSN: None     Source Type: Journal    
DOI: 10.1089/nat.2013.0461     Document Type: Review

References (133)

1. AARTSMA-RUS, A., KAMAN, W.E., BREMMER-BOUT, M., JANSON, A.A., DEN DUNNEN, J.T., VAN OMMEN, G.and VAN DEUTEKOM, J.C. (2004). Comparative analysis of antisense oligonucleotide analogs for targeted DMD exon 46 skipping in muscle cells. Gene Ther 11, 1391-1398.
2. AARTSMA-RUS, A., and VAN OMMEN, G.J. (2009). Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. RNA. 13, 1609-1624.
3. AARTSMA-RUS, A. (2012). Overview on DMD exon skipping. In: Exon Skipping. A. Aartsma-Rus, ed. Methods Mol. Biol. 867, 97-116.
4. ABES, S., MOULTON, H.M., CLAIR, P., PREVOT, P., YOUNGBLOOD, D.S., WU, R.P., IVERSEN, P.L., and LEBLEU, B. (2006). Vectorization of morpholino oligomers by the (R-Ahx-R)(4) peptide allows efficient splicing correction in the absence of endosomolytic agents. J. Control. Release 116, 304-113.
5. 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.
6. 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.
7. ANDREADIS, A. (2012). Tau splicing and the intricacies of dementia. J. Cell. Physiol. 227, 1220-1225.
8. ARECHAVALA-GOMEZA, V., ANTHONY, K., MORGAN, J., and MUNTONI, F. (2012). Antisense oligonucleotidemediated exon skipping for Duchenne muscular dystrophy: progress and challenges. Curr. Gene Ther. 12, 52-60.
9. ARZUMANOV, A., WALSH, A.P., RAJWANSHI, V.K., KUMAR, R., WENGEL, J., and GAIT, M.J. (2001). Inhibition of HIV-1 Tat-dependent trans-activation by steric block chimeric 2¢-O-methyl/LNA oligoribonucleotides. Biochemistry 40, 14645-14654.
10. BAKKENIST, C.J., and KASTAN, M.B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 421, 499-506.
11. BANKS, W.A., FARR, S.A., BUTT, W., KUMAR, V.B., FRANKO, M.W., and MORLEY, J.E. (2001). Delivery across the blood-brain barrier of antisense directed against amyloid beta: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein. J. Pharmacol. Exp. Ther. 297, 1113-1121.
12. BELTRAMI, S., KIM, R., and GORDON, J. (2013). Neurofibromatosis type 2 protein, NF2: an uncoventional cell cycle regulator. Anticancer Res. 33, 1-11.
13. BONNET-DUPEYRON, M.N., COMBES, P., SANTANDER, P., CAILLOUX, F., and BOESPFLUG-TANGUY, O. (2008). PLP1 splicing abnormalities identified in Pelizaeus-Merzbacher disease and SPG2 fibroblasts are associated with different types of mutations. Hum. Mutat. 29, 1028-1036.
14. BURRER, R., NEUMAN, B.W., TING, J.P.C., STEIN, D.A., MOULTON, H.M., IVERSEN, P.L., KUHN, P., and BUCHMEIER, M.J. (2007). Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. J. Virol. 81, 5637-5648.
15. CARROLL, J.B., WARBY, S.C., SOUTHWELL, A.L., DOTY, C.N., GREENLEE, S., SKOTTE, N., HUNG, G., BENNETT, C.F., FREIER, S.M., and HAYDEN, M.R. (2011). Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele-specific silencing of mutant huntingtin. Mol. Ther. 19, 2178-2185.
16. CASTELLANOS, E., ROSAS, I., SOLANES, A., BIELSA, I., LÁ ZARO, C., CARRATO, C., HOSTALOT, C., PRADES, P., ROCA-RIBAS, F., BLANCO, I., and SERRA, E; NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC. (2013). In vitro antisense therapeutics for a deep intronic mutation causing Neurofibromatosis type 2. Eur. J. Hum. Genet. 21, 769-73.
17. CAVALIERI, S., POZZI, E., GATTI, R.A., and BRUSCO, A. (2013). Deep-intronic ATM mutation detected by genomic resequencing and corrected in vitro by antisense morpholino oligonucleotide (AMO). Eur. J. Hum. Genet. 21, 774-778.
18. CHAUHAN, N.B. (2002). Trafficking of intracerebroventricularly injected antisense oligonucleotides in the mouse brain. Antisense Nucleic Acid Drug Dev. 12, 353-357.
19. CHAUHAN, N.B. and SIEGEL, G.J. (2007). Antisense inhibition at the b secretase-site of b-amyloid precursor protein reduces cerebral amyloid and acetyl cholinesterase activity in Tg2576. Neuroscience 146, 143-151.
20. CHEN, Y., and LIU, L. (2012). Modern methods for delivery of drugs across the blood-brain barrier. Adv. Drug Deliv. Rev. 64, 640-665.
21. CIRAK, S., ARECHAVALA-GOMEZA, V., GUGLIERI, M., FENG, L., TORELLI, S., ANTHONY, K., 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, doseescalation study. Lancet. 378, 595-605.
22. DAWSON, H.N., CANTILLANA, V., CHEN, L., and VITEK, M.P. (2007). The tau N279K exon 10 splicing mutation recapitulates Frontotemporal Dementia and Parkinsonism linked to chromosome 17 tauopathy in a mouse model. J. Neurosci. 27, 9155-9168.
23. DE CLERCQ, E., ECKSTEIN, F., STERNBACH, H., and MERIGAN, T.C. (1969). Interferon induction by and ribonuclease sensitivity of thiophosphate- substituted polyribonucleotides. Antimicrob. Agents Chemother. (Bethesda) 9, 187-191.
24. DHIR, A., and BURATTI, E. (2010). Alternative splicing: role of pseudoexons in human disease and potential therapeutic strategies. FEBS J 277, 841-855.
25. DHURIA, S.V., HANSON, L.R., and FREY, W.H., 2nd (2010). Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J. Pharm. Sci. 99, 1654-1673.
26. DISTERER, P. and KHOO, B. (2012). Antisense-mediated exon-skipping to induce gene knockdown. In: Exon Skipping. Annemieke Aartsma-Rus, ed. Methods Mol. Biol. 867, 289-306.
27. DONAHUE, C.P., MURATORE, C., WU, J.Y., KOSIK, K.S., and WOLFE, M.S. (2006). Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing. J. Biol. Chem. 281, 23302-23306.
28. DOUGLAS A.G.L., and WOOD M.J.A. (2013). Splicing therapy for neuromuscular disease. Mol. Cell. Neurosci. 56, 169-185.
29. DU, L., POLLARD, J.M., and GATTI, R.A. (2007). Correction of prototypic ATM splicing mutations and aberrant ATM function with antisense morpholino oligonucleotides. Proc. Natl. Acad. Sci. U. S. A. 104, 6007-6012.
30. DU, L., KAYALI, R., BERTONI, C., FIKE, F., HU, H., IVERSEN, P.L., and GATTI, R.A. (2011). Arginine-rich cellpenetrating peptide dramatically enhances AMO-mediated ATM aberrant splicing correction and enables delivery to brain and cerebellum. Hum. Mol. Genet. 20, 3151-3160.
31. DUARRI, A., TEIJIDO, O., LÓ PEZ-HERNÁ NDEZ, T., SCHEPER, G.C., BARRIERE, H., BOOR, I., AGUADO, F., ZORZANO, A., PALACÍN, M., MARTÍNEZ, A., et al. (2008). Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. Hum. Mol. Genet. 17, 3728-3739.
32. DUNCKLEY, M.G., MANOHARAN, M., VILLIET, P., EPERON, I.C., and DICKSON, G. (1998). Modification of splicing in the dystrophin gene in cultured mdx muscle cells by antisense oligoribonucleotides. Hum. Mol. Genet. 7, 1083-1090.
33. DUPRÉ , T., BARNIER, A., DE LONLAY, P., CORMIERDAIRE, V., DURAND, G., CODOGNO, P., and SETA N. (2000). Defect in N-glycosylation of proteins is tissuedependent in congenital disorders of glycosylation ia. Glycobiology 10, 1277-1128.
34. EGHOLM, M., BUCHARDT, O., CHRISTENSEN, L., BEHRENS, C., FREIER, S.M., DRIVER, D.A. BERG, R.H., KIM, S.K., NORDÉ N, B., and NIELSEN, P.E. (1993). PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen bonding rules. Nature 365, 566-568.
35. ELAYADI, A.N., BRAASCH, D.A., and COREY, D.R. (2002). Implications of high-affinity hybridization by locked nucleic acid oligomers for inhibition of human telomerase. Biochemistry 41, 9973-9981.
36. ERICKSON, M.A., NIEHOFF, M.L., FARR, S.A., MORLEY, J.E., DILLMAN, L.A., LYNCH, K.M., and BANKS, W.A. (2012). Peripheral administration of antisense oligonucleotides targeting the amyloid-ß protein precursor reverses AßPP and LRP-1 overexpression in the aged SAMP8 mouse brain. J. Alzheimers Dis. 28, 951-960.
37. FABANI, M., and GAIT, M.J. (2008). miR-122 targeting with LNA/2¢-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA peptide conjugates. RNA 14, 336-346.
38. FERLINI, A., SABATELLI, P., FABRIS, M., BASSI, E., FALZARANO, S., VATTEMI, G., PERRONE, D., GUALANDI, F., MARALDI, N.M., MERLINI, L., 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.
39. FERNÁ NDEZ-RODRÍGUEZ, J., CASTELLSAGUÉ , J., BENITO, L., BENAVENTE, Y., CAPELLÁ , G., BLANCO, I., SERRA, E. and LÁ ZARO, C. (2011). A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism. Hum. Mutat. 32, 705-709.
40. FIORINI, A., SULTANA, R., FÖ RSTER, S., PERLUIGI, M., CENINI, G., CINI C., CAI, J., KLEIN, J.B., FARR, S.A., NIEHOFF, M.L., et al. (2013). Antisense directed against PS-1 gene decreases brain oxidative markers in aged senescence accelerated mice (SAMP8) and reverses learning and memory impairment: A proteomics study. Free Radic. Biol. Med. 15, 65C:1-14.
41. FLETCHER, S., HONEYMAN, K., FALL, A.M., HARDIN, P.L., JOHNSEN, R.D., 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.
42. FLUITER, K., TEN ASBROEK, A.L., DE WISSEL, M.B., JAKOBS, M.E., WISSENBACH, M., OLSSON, H., OLSEN, O., OERUM, H., and BAAS, F. (2003). In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides. Nucl. Acids Res. 31, 953-962.
43. FRIEDMAN, J.M. (1999). Epidemiology of neurofibromatosis type 1. Am. J. Med. Genet. 89, 1-6.
44. GARBERN, J.Y. (2007). Pelizaeus-Merzbacher disease: genetic and cellular pathogenesis. Cell. Mol. Life Sci. 64, 50-65.
45. 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.
46. GOEMANS, N.M., TULINIUS, M., VAN DEN AKKER, J.T., BURM, B.E., EKHART, P.F., HEUVELMANS, N,. et al. (2011). Systemic administration of PRO051 in Duchenne's muscular dystrophy. N. Engl. J. Med. 364, 1513-1522.
47. GRÜ NEWALD, S., HUYBEN, K., DE JONG, J.G., SMEITINK, J.A., RUBIO, E., BOERS, G.H, CONRADT, HS., WENDEL, U., and WEVERS, R.A. (1999). Beta-trace protein in human cerebrospinal fluid: a diagnostic marker for N-glycosylation defects in brain. Biochim. Biophys. Acta. 1455, 54-60.
48. GUTMANN, D.H., PARADA, L.F., SILVA, A.J., and RATNER, N. (2012). Neurofibromatosis type 1: modeling CNS dysfunction. J. Neurosci. 32, 14087-14093.
49. HEEMSKERK, H.A., DE WINTER, C.L., DE KIMPE, S.J., VAN KUIK-ROMEIJN, P., HEUVELMANS, N., PLATENBURG, G., VAN OMMEN, G.J., VAN DEUTEKOM, J.C., and AARTSMA-RUS, A. (2009). In vivo comparison of 2¢-Omethyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J. Gene Med. 11, 257-266.
50. HOBSON GM, HUANG Z, SPERLE K, STABLEY DL, MARKS HG, and CAMBI F. (2002). A PLP splicing abnormality is associated with an unusual presentation of PMD. Ann. Neurol. 52, 477-488.
51. HOYER, J., and NEUNDORF, I. (2012). Peptide vectors for the nonviral delivery of nucleic acids. Acc. Chem. Res. 45, 1048-1056.
52. HSUEH, Y.P. (2012). From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation. J. Biomed. Sci. 19, 33.
53. HUA, Y., VICKERS, T.A., BAKER, B.F., BENNETT, C.F., and KRAINER, A.R. (2007). Enhancement of SMN2 Exon 7 inclusion by antisense oligonucleotides targeting the exon. PLoS Biol 5, e73.
54. HUA, Y., SAHASHI, K., RIGO, F., HUNG, G., HOREV, G., BENNETT, C.F., and KRAINER, A.R. (2011). Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature 478, 123-126.
55. HUA, Y., SAHASHI, K., HUNG, G., RIGO, F., PASSINI, M.A., BENNETT, C.F., and KRAINER, A.R. (2010). Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 24, 1634-1644.
56. HUA Y., and KRAINER A.R. (2012). Antisense-mediated exon inclusion. In Exon Skipping: Methods and Protocols. Aartsma-Rus A., ed. Methods in Molecular Biology, 867, 307-323.
57. HÜ BNER CA, SENNING A, ORTH U, ZERRES K, URBACH H, GAL A, and RUDNIK-SCHÖ NEBORN S. (2002). Mild Pelizaeus-Merzbacher disease caused by a point mutation affecting correct splicing of PLP1 mRNA. Neuroscience. 132, 697-701.
58. 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.
59. JOHNSON, M.B., KAWASAWA, Y.I., MASON, C.E., KRSNIK, Z., COPPOLA, G., BOGDANOVIĆ , D., GESCHWIND, D.H., MANE, S.M., STATE, M.W., and SESTAN, N. (2009). Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62, 494-509.
60. KALBFUSS, B., MABON, S.A., and MISTELI, T. (2001). Correction of alternative splicing of tau in frontotemporal dementia and parkinsonism linked to chromosome 17. J. Biol. Chem. 276, 42986-42993.
61. KANAZAWA, T., AKIYAMA, F., KAKIZAKI, S., TAKASHIMA, Y., and SETA, Y. (2013). Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cellpenetrating peptide-modified nano-micelles. Biomaterials 34, 9220-9226.
62. KANG, S.-H., CHO, M.-J., and KOLE, R. (1998). Up-regulation of luciferase gene expression with antisense oligonucleotides: implications and applications in functional assay development. Biochemistry 37, 6235-6239.
63. KARRAS, J.G., MCKAY, R.A., DEAN, N.M., and MONIA, B.P. (2000). Deletion of individual exons and induction of soluble murine interleukin-5 receptor alpha chain expression through antisense oligonucleotide-mediated redirection of premRNA splicing. Mol. Pharmacol. 58, 380-387.
64. KARRAS, J.G., MAIER, M.A., LU, T., WATT, A., and MANOHARAN, M. (2001). Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine interleukin-5 receptor-a chain. Biochemistry 40, 7853-7859.
65. KHEDER, A., SCOTT, C., OLPIN, S., and HADJIVASSILIOU, M. (2013). Niemann-Pick type C: a potentially treatable disorder? Pract. Neurol. 13, 382-385. doi: 10.1136/practneurol-2013-000525.
66. KINALI, M., ARECHAVALA-GOMEZA, V., FENG, L., CIRAK, S., HUNT, D., ADKIN, C., 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-ofconcept study. Lancet Neurol. 8, 918-928.
67. KORDASIEWICZ, H.B., STANEK, L.M., WANCEWICZ, E.V., MAZUR, C., MCALONIS, M.M., PYTEL, K.A., ARTATES, J.W., WEISS, A., CHENG, S.H., SHIHABUDDIN, L.S., et al. (2012). Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 74, 1031-1044.
68. KUMAR, V.B., FARR, S.A., FLOOD, J.F., KAMLESH, V., FRANKO, M., BANKS, W.A., and MORLEY, J.E. (2000). Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice Peptides 21, 1769-1775.
69. LARSEN, H.J., BENTIN, T., and NIELSEN, P.E. (1999). Antisense properties of peptide nucleic acid. Biochim. Biophys. Acta 1489, 159-166.
70. LASSUTHOVA ́ , P., ZALIOVA ́ ,M., INOUE, K., HABERLOVÁ , J., SIXTOVÁ , K., SAKMARYOVÁ, I., PADEROVA ́ , K., MAZANEC, R., ZA ́ MECNÍK, J., SISKOVÁ , D., et al. ( 2013). Three new PLP1 splicing mutations demonstrate pathogenic and phenotypic diversity of Pelizaeus-Merzbacher disease. J. Child Neurol. 2013, Jun 14. [ Epub ahead of print]
71. LEE, Y., EL ANDALOUSSI, S., and WOOD, M.J. (2012). Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum. Mol. Genet. 21, R125-R134.
72. LI, Y.F., and MORCOS, P.A. (2008). Design and synthesis of dendritic molecular transporter that achieves efficient in vivo delivery of morpholino antisense oligo. Bioconjug. Chem. 19, 1464-1470.
73. LU, Q.L., MANN, C.J., LOU, F., BOU-GHARIOS, G., MORRIS, G.E., XUE, S.A., FLETCHER, S., PARTRIDGE, T.A., and WILTON, S.D. (2003). Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med. 9, 1009-1014.
74. LU, Q.L., RABINOWITZ, A., CHEN, Y.C., YOKOTA, T., YIN, H., ALTER, J., JADOON, A., BOU-GHARIOS, G., and PARTRIDGE, T. (2005). Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc. Natl. Acad. Sci. U. S. A. 102, 198-203.
75. MACÍAS-VIDAL, J., RODRÍGUEZ-PASCAU, L., SÁ NCHEZOLLE ́ , G., LLUCH, M., VILAGELIU, L., GRINBERG D., and COLL, M.J.; SPANISH NPC WORKING GROUP. (2011). Molecular analysis of 30 Niemann-Pick type C patients from Spain. Clin. Genet. 80, 39-49.
76. MANCINI, C., VAULA, G., SCALZITTI, L., CAVALIERI, S., BERTINI, E., AIELLO, C., LUCCHINI, C., GATTI, R.A., BRUSSINO, A., and BRUSCO, A. (2012). Megalencephalic leukoencephalopathy with subcortical cysts type 1 (MLC1) due to a homozygous deep intronic splicing mutation (c.895-226T > G) abrogated in vitro using an antisense morpholino oligonucleotide. Neurogenetics 13, 205-14.
77. MANOHARAN, M. (1999). 2¢-Carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochim. Biophys. Acta 1489, 117-130.
78. MASSERINI, M. (2013). Nanoparticles for Brain Drug Delivery. ISRN Biochemistry. doi:10.1155/2013/238428.
79. MATLIN, A.J., CLARK, F., and SMITH, C.W.J. (2005). Understanding alternative splicing: Towards a cellular code. Nat. Rev. Mol. Cell Biol. 6, 386-398.
80. MIAO, N., LU X., O'GRADY, N.P., YANJANIN, N., PORTER, F.D., and QUEZADO, Z.M. (2012). Niemann-pick disease type C: implications for sedation and anesthesia for diagnostic procedures. J. Child Neurol. 27, 1541-1546.
81. MILLER, T.M., PESTRONK, A., DAVID, W., ROTHSTEIN, J., SIMPSON, E., APPEL, S.H., ANDRES, P.L., MAHONEY, K., ALLRED, P., ALEXANDER, K., et al. (2013). An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 5, 435-442.
82. MILLS, J.D., and JANITZ, M. (2012). Alternative splicing of mRNA in the molecular pathology of neurodegenerative diseases. Neurobiol. Aging 33, 1012.e11-1012.e24.
83. MUKHERJEE, S., and MAXFIELD, F.R. (2004). Lipid and cholesterol trafficking in NPC. Biochim. Biophysic. Acta 1685, 28-37.
84. NAKAMURA, K., DU, L., TUNUGUNTLA, R., FIKE, F., CAVALIERI, S., MORIO, T., MIZUTANI, S., BRUSCO, A., and GATTI, R.A. (2012). Functional characterization and targeted correction of ATM mutations identified in Japanese patients with ataxia-telangiectasia. Hum. Mutat. 33, 198-208.
85. NAVE, K.A., LAI, C., BLOOM, F.E., and MILNER, R.J. (1987). Splice site selection in the proteolipid protein (PLP) gene transcript and primary structure of the DM-20 protein of central nervous system myelin. Proc. Natl. Acad. Sci. U. S. A. 84, 5665-5669.
86. OBIKA, S., NANBU, D., HARI, Y. ANDOH, I., MORIO, K., DOI, T. and IMANISHI, T. (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.
87. PASSINI, M.A, BU, J., RICHARDS A.M, KINNECOM, C., SARDI, S.P., STANEK, L.M., HUA, Y., RIGO F., MATSON J., HUNG, G., et al. (2011). Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci. Transl. Med.3, 72ra18.
88. PEACEY, E., RODRIGUEZ, L., LIU, Y., and WOLFE, M.S. (2012). Targeting a pre-mRNA structure with bipartite antisense molecules modulates tau alternative splicing. Nucleic Acids Res. 40, 9836-9849.
89. PEARL, P.L., and KRASNEWICH, D. (2001). Neurologic course of congenital disorders of glycosylation J. Child Neurol. 16, 409-413.
90. PÉREZ-MARTÍNEZ, F.C., GUERRA, J., POSADAS, I., and CEÑ A, V. (2011). Barriers to non-viral vector-mediated gene delivery in the nervous system. Pharm Res. 28, 1843-1858.
91. PERLMAN, S., BECKER-CATANIA, S., and GATTI, R.A. (2003). Ataxia-telangiectasia: diagnosis and treatment. Semin. Pediatr. Neurol. 10, 173-182.
92. POHL, S., HOFFMANN, A., RÜ DIGER, A., NIMTZ, M., JAEKEN, J., and CONRADT, H.S. (1997). Hypoglycosylation of a brain glycoprotein (b-trace protein) in CDG syndromes due to phosphomannomutase deficiency and N-acetylglucosaminyl-transferase II deficiency. Glycobiology 7, 1077-1084.
93. PORENSKY, P., and BURGHES, A. (2013). Antisense oligonucleotides for the treatment of Spinal Muscular Atrophy. Hum. Gene Ther. 24, 489-498.
94. PORENSKY, P.N., MITRPANT, C., MCGOVERN, V.L., BEVAN, A.K., FOUST, K.D., KASPAR, B.K., WILTON, S.D., and BURGHES, A.H. (2012). A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in the mouse. Hum. Mol. Genet. 21, 1625-1638.
95. PROS, E., GÓ MEZ, C., MARTÍN, T., FÁ BREGAS, P., SERRA, E., and LÁ ZARO, C. (2008). Nature and mRNA effect of 282 different NF1 point mutations: focus on splicing alterations. Hum. Mutat. 29, 173-193.
96. PROS, E., FERNÁ NDEZ-RODRÍGUEZ,J., CANET, B., BENITO, L., SÁ NCHEZ, A., BENAVIDES, A., RAMOS, F.J., LÓ PEZ-ARIZTEGUI, M.A., CAPELLÁ , G., BLANCO, I., et al. (2009). Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations. Hum. Mutat. 30, 454-462.
97. REGIS, S., CORSOLINI, F., GROSSI, S., TAPPINO, B., COOPER, D.N., and FILOCAMO, M. (2013). Restoration of the normal splicing pattern of the PLP1 gene by means of an antisense oligonucleotide directed against an exonic mutation. PLoS One 8, e73633.
98. RENNER, D.B., FREY, W.H. 2nd, and HANSON, L.R. (2012). Intranasal delivery of siRNA to the olfactory bulbs of mice via the olfactory nerve pathway. Neurosci. Lett. 513, 193-197.
99. RIMESSI, P., SABATELLI, P., FABRIS, M., BRAGHETTA, P., BASSI, E., SPITALI, P., VATTEMI, G., TOMELLERI, G., MARI, L., PERRONE, D., et al. (2009). Cationic PMMA nanoparticles bind and deliver antisense oligoribonucleotides allowing restoration of dystrophin expression in the mdx mouse. Mol. Ther. 17, 820-827.
100. ROBERTS, J., PALMA, E., SAZANI, P., ∅RUM, H., CHO, M., and KOLE, R. (2006). Efficient and persistent splice switching by systemically delivered LNA oligonucleotides in mice. Mol. Ther. 14, 471-475.
101. RODRÍGUEZ-PASCAU, L., COLL, M.J., VILAGELIU, L., and GRINBERG, D. (2009). Antisense oligonucleotide treatment for a pseudoexon-generating mutation in the NPC1 gene causing Niemann-Pick type C disease. Hum. Mutat. 30, E993-E1001.
102. SALEH, A.F., ARZUMANOV, A.A., and GAIT M.J. (2012). Overview of alternative oligonucleotide chemistries for exon skipping. In: Exon Skipping. A. Aartsma-Rus, ed. Methods Mol. Biol. 867, 365-378.
103. SAZANI, P., KANG, S.-H., MAIER, M.A., WEI, C., DILLMAN, J., SUMMERTON, J., MANOHARAN, M., and KOLE, R. (2001). Nuclear antisense effects of neutral, anionic and cationic analogs. Nucleic Acids Res. 29, 3965-3974.
104. SAZANI, P., GEMIGNANI, F., KANG, S.H., MAIER, M.A., MANOHARAN, M., PERSMARK, M., BORTNER, D., and KOLE, R. (2002). Systemically delivered antisense oligomers upregulate gene expression in mouse tissues. Nat. Biotechnol. 20, 1228-1233.
105. SCHMAJUK, G., SIERAKOWSKA, H., and KOLE, R. (1999). Antisense oligonucleotides with different backbones. Modification of splicing pathways and efficacy of uptake. J. Biol. Chem. 274, 21783-21789.
106. SCHOLLEN, E., KELDERMANS, L., FOULQUIER, F., BRIONES, P., CHABAS, A., SÁ NCHEZ-VALVERDE, F., ADAMOWICZ, M., PRONICKA, E., WEVERS, R., and MATTHIJS, G. (2007). Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. Mol. Genet. Metab. 90, 408-413.
107. SIERAKOWSKA, H., SAMBADE, M.J., AGRAWAL, S., and KOLE, R. (1996). Repair of thalassemic human b-globin mRNA in mammalian cells by antisense oligonucleotides. Proc. Natl. Acad. Sci. U. S. A. 93, 12840-12844.
108. SMITH, R.A., MILLER, T.M., YAMANAKA, K., MONIA, B.P., CONDON, T.P., HUNG, G., LOBSIGER, C.S., WARD, C.M., MCALONIS-DOWNES, M., WEI, H., et al. (2006). Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Invest. 116, 2290-2296.
109. SOUTHWELL, A.L., SKOTTE, N.H., BENNETT, C.F., and HAYDEN, M.R. (2012). Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases. Trends Mol. Med. 18, 634-643.
110. SPROAT, B.S., LAMOND, A.I., BEIJER, B., NEUNER, P., and RYDER, U. (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.
111. SUMMERTON, J.E. (2005). Endo-Porter: a novel reagent for safe, effective delivery of substances into cells. Ann. N. Y. Acad. Sci. 1058, 62-75.
112. SUMMERTON, J.E., and WELLER, D. (1997). Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 7, 187-195.
113. SWAYZE, E.E., SIWKOWSKI, A.M., WANCEWICZ, E.V., MIGAWA, M.T., WYRZYKIEWICZ T.K., HUNG, G., MONIA, B.P. and BENNETT, C.F. (2007). Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals. Nucleic Acids Res. 35, 687-700.
114. TERAOKA, S.N.,TELATAR, M., BECKER-CATANIA, S., LIANG, T., ONENGÜ T, S., TOLUN, A., CHESSA, L., SANAL, O., BERNATOWSKA, E., GATTI, and R.A., CONCANNON, P. (1999). Splicing defects in the ataxiatelangiectasia gene, ATM: underlying mutations and consequences. Am. J. Hum. Genet. 64, 1617-1631.
115. TSUBOI, Y. (2009). Clinical, pathological, and genetic characteristics of frontotemporal dementia and parkinsonism linked to chromosome 17 with mutations in the MAPT and PGRN. Brain Nerve. 11, 1285-1291.
116. TURCZYNSKI, S., TITEUX, M., PIRONON, N., and HOVNANIAN, A. (2012). Antisense-mediated exon skipping to reframe transcripts. In: Exon Skipping. A. Aartsma-Rus. ed. Methods Mol. Biol. 867, 221-238.
117. UMEDA, T., YAMASHITA, T., KIMURA. T., OHNISHI, K., TAKUMA, H., OZEKI, T., TAKASHIMA, A., TOMIYAMA, T., and MORI, H. (2013). Neurodegenerative disorder FTDP-17-related tau intron 10 + 16C > T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice. Am. J. Pathol. 183, 211-225.
118. VAN DEUTEKOM, J.C., JANSON, A.A., GINJAAR, I.B., FRANKHUIZEN, W.S., AARTSMA-RUS, A., BREMMERBOUT, M., et al. (2007). Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 357, 2677-2686.
119. VAN ROON-MOM W.M.C. and AARTSMA-RUS A. (2012). Overview on applications of antisense-mediated exon skipping. In: Exon Skipping. A. Aartsma-Rus, ed. Methods Mol. Biol. 867, 79-96.
120. VEGA, A.I., PÉREZ-CERDÁ , C., DESVIAT, L.R., MATTHIJS, G., UGARTE, M., and PÉ REZ, B. (2009). Functional analysis of three splicing mutations identified in the PMM2 gene: toward a new therapy for congenital disorder of glycosylation type 1a. Hum. Mutat. 30,795-803.
121. VICKERS, T.A., ZHANG, H., GRAHAM, M.J., LEMONIDIS, K.M., ZHAO, C., and DEAN, N.M. (2006). Modification of MyD88 mRNA splicing and inhibition of IL-1 signaling in cell culture and in mice with a 2¢-O-methoxyethyl-modified oligonucleotide. J. Immunol. 176, 3652-3661.
122. VUILLAUMIER-BARROT, S., LE BIZEC, C., DE LONLAY, P., MADINIER-CHAPPAT, N., BARNIER, A., DUPRE, T., DURAND, G., and SETA, N. (2006). PMM2 intronic branchsite mutations in CDG-Ia. Mol. Genet. Metab. 87, 337-340.
123. WINER, L., SRINIVASAN, D., CHUN S. et al. (2013). SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy. JAMA Neurol., 70, 201-207
124. WONG, H.L., WU, X.Y., and BENDAYAN, R. (2012). Nanotechnological advances for the delivery of CNS therapeutics. Adv. Drug Deliv. Rev. 64, 686-700.
125. WOODWARD, K.J. (2008). The molecular and cellular defects underlying Pelizaeus-Merzbacher disease. Expert Rev. Mol. Med. 19, 10.
126. WU, B., MOULTON, H.M., P.L., IVERSEN, JIANG, J., LI, J., LI, J., SPURNEY, C.F., SALI, A., GUERRON, A.D., NAGARAJU, K., et al. (2008). Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc. Natl. Acad. Sci. U. S. A. 105, 14814-14819.
127. 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.
128. WU, B., LI, Y.-F., MORCOS, P.A., 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.
129. YIN, H., LU, Q., and WOOD, M.J. (2008a). Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx mice. Mol. Ther. 16, 38-45.
130. YIN, H., MOULTON, H.M., SEOW, Y., BOYD, C., BOUTILIER, J., IVERSON, P., and WOOD, M.J. (2008b). Cellpenetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Hum. Mol. Genet. 17, 3909-3918.
131. 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.
132. YIN, H., SALEH, A.F., BETTS, C., CAMILETTI, P., SEOW, Y., ASHRAF, S., ARZUMANOV, A.and WOOD, M.J. (2011). Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic correction in mdx mice. Mol. Ther. 19, 1295-1303.
133. YIN, H., BETTS, C., SALEH, A.F., IVANOVA, G.D., LEE, H., SEOW, Y., KIM, D., GAIT, M.J., and WOOD, MJ. (2010). Optimization of peptide nucleic acids antisense oligonucleotides for local and systemic dystrophin splice correction in the mdx mouse. Mol. Ther. 18, 819-827