Antisense modulation of both exonic and intronic splicing motifs induces skipping of a DMD pseudo-exon responsible for X-linked dilated cardiomyopathy

Human Gene Therapy

Volumn 21, Issue 9, 2010, Pages 1137-1146

  Rimessi, Paola ^a   Fabris, Marina ^a   Bovolenta, Matteo ^a   Bassi, Elena ^a   Falzarano, Sofia ^a   Gualandi, Francesca ^a   Rapezzi, Claudio ^b   Coccolo, Fabio ^b   Perrone, Daniela ^a   Medici, Alessandro ^a   Ferlini, Alessandra ^a  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DESMIN; DYSTROPHIN; MYOSIN;

ANTISENSE THERAPY; ARTICLE; CARDIOMYOPATHY; DNA SEQUENCE; EXON; GENE DELETION; GENE MUTATION; HUMAN; HUMAN TISSUE; IN VITRO STUDY; INTRON; NUCLEOTIDE SEQUENCE; RNA SEQUENCE; RNA SPLICING; X LINKED DILATED CARDIOMYOPATHY;

BASE SEQUENCE; BIOLOGICAL ASSAY; CARDIOMYOPATHY, DILATED; CELL-FREE SYSTEM; DYSTROPHIN; EXONS; FIBROBLASTS; FLUORESCENT ANTIBODY TECHNIQUE; GENETIC DISEASES, X-LINKED; HUMANS; INTRONS; MOLECULAR SEQUENCE DATA; MUSCLE CELLS; MYOD PROTEIN; OLIGONUCLEOTIDES, ANTISENSE; REGULATORY SEQUENCES, NUCLEIC ACID; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA SPLICING; TRANSFORMATION, GENETIC;

EID: 77957850598     PISSN: 10430342     EISSN: None     Source Type: Journal    
DOI: 10.1089/hum.2010.010     Document Type: Article

References (51)

1. Aartsma-Rus, A., and Van Ommen, G.J. (2007). Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications. RNA 13, 1609-1624.
2. 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. (2004). Antisense-induced multiexon skipping for Du-chenne muscular dystrophy makes more sense. Am. J. Hum. Genet. 74, 83-92.
3. Aartsma-Rus, A., Janson, A.A., Heemskerk, J.A., De Winter, C.L., Van Ommen, G.J., and Van Deutekom, J.C. (2006a). Therapeutic modulation of DMD splicing by blocking exonic splicing enhancer sites with antisense oligonucleotides. Ann. N. Y. Acad. Sci. 1082, 74-76.
4. 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, 135-144.
5. Aartsma-Rus, A., Van Vliet, L., Hirschi, M., Janson, A.A., Heemskerk, H., De Winter, C.L., De Kimpe, S., Van Deutekom, J.C., T'Hoen, P.A, and Van Ommen, G.J. (2009). Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms. Mol. Ther. 17, 548-553.
6. Baralle, D., and Baralle, M. (2005). Splicing in action: Assessing disease causing sequence changes. J. Med. Genet. 42, 737-748.
7. Barnard, D.C., Li, J., Peng, R., and Patton, J.G. (2002). Regulation of alternative splicing by SRrp86 through coactivation and repression of specific SR proteins. RNA 8, 526-533.
8. Béroud, C., Carrié, A., Beldjord, C., Deburgrave, N., Llense, S., Carelle, N., Peccate, C., Cuisset, J.M., Pandit, F., Carré-Pigeon, F., Mayer, M., Bellance, R., Récan, D., Chelly, J., Kaplan, J.C., and Leturcq, F. (2004). Dystrophinopathy caused by mid-intronic substitutions activating cryptic exons in the DMD gene. Neuromuscul. Disord. 14, 10-18.
9. Black, D.L. (2003). Mechanisms of alternative pre-messenger RNA splicing [review]. Annu. Rev. Biochem. 72, 291-336.
10. 0 splice site activation. Mol. Cell. Biol. 19, 7347-7356.
11. Buratti, E., Baralle, M., and Baralle, F.E. (2006). Defective splicing, disease and therapy: Searching for master checkpoints in exon definition. Nucleic Acids Res. 34, 3494-3510.
12. Caceres, J.F., Stamm, S., Helfman, D.M., and Krainer, A.R. (1994). Regulation of alternative splicing in vivo by over-expression of antagonistic splicing factor. Science 265, 1706-1709.
13. Cartegni, L., Wang, J., Zhu, Z., Zhang, M.Q., and Krainer, A.R. (2003). ESEfinder: A web resource to identify exonic splicing enhancers. Nucleic Acids Res. 31, 3568-3571.
14. Chandler, S.D., Mayeda, A., Yeakley, J.M., Krainer, A.R., and Fu, X.D. (1997). RNA splicing specificity determined by the coordinated action of RNA recognition motifs in SR proteins. Proc. Natl. Acad. Sci. U.S.A. 94, 3596-3601.
15. Cohen, N., Rimessi, P., Gualandi, F., Ferlini, A., and Muntoni, F. (2004). In vivo study of an aberrant dystrophin exon inclusion in X-linked dilated cardiomyopathy. Biochem. Biophys. Res. Commun. 317, 1215-1220.
16. Desmet, F.O., Desmet, F.O., Hamroun, D., Lalande, M., Collod-Béroud, G., Claustres, M., and Béroud, C. (2009). Human Splicing Finder: An online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 37, e67.
17. 0 splice sites: role of U1 snRNP and models for the antagonistic effects of SF2/ASF and hnRNP A1. Mol. Cell. Biol. 20, 8303-8318.
18. Errington, S.J., Mann, C.J., Fletcher, S., and Wilton, S.D. (2003). Target selection for antisense oligonucleotide induced exon skipping in the dystrophin gene. J. Gene Med. 5, 518-527. (Pubitemid 40310395)
19. Fairbrother, W.G., Yeh, R.F., Sharp, P.A., and Burge, C.B. (2002). Predictive identification of exonic splicing enhancers in human genes. Science 297, 1007-1013.
20. Ferlini, A., Galie, N., Merlini, L., Sewry, C., Branzi, A., and Muntoni, F. (1998). A novel Alu-like element rearranged in the dystrophin gene causes a splicing mutation in a family with X-linked dilated cardiomyopathy. Am. J. Hum. Genet. 63, 436-446.
21. Fischer, D.C., Noack, K., Runnebaum, I.B., Watermann, D.O., Kieback, D.G., Stamm, S., and Stickeler, E. (2004). Expression of splicing factors in human ovarian cancer. Oncol. Rep. 11, 1085-1090.
22. Gualandi, F., Trabanelli, C., Rimessi, P., Calzolari, E., Toffolatti, L., Patarnello, T., Kunz, G., Muntoni, F., and Ferlini, A. (2003). Genomic definition of a pure intronic dystrophin deletion responsible for an XLDC splicing mutation: In vitro mimicking and antisense modulation of the splicing abnormality. Gene 311, 25-33.
23. Gurvich, O.L., Tuohy, T.M., Howard, M.T., Finkel, R.S., Medne, L., Anderson, C.B., Weiss, R.B., Wilton, S.D., and Flanigan, K.M. (2008). DMD pseudoexon mutations: Splicing efficiency, phenotype, and potential therapy. Ann. Neurol. 63, 81-89.
24. Highsmith, W.E., Burch, L.H., Zhou, Z., Olsen, J.C., Boat, T.E., Spock, A., Gorvoy, J.D., Quittell, L., Friedman, K.J., Silverman, L.M., Boucher, R.C., and Knowles, M.R. (1994). A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N. Engl. J. Med. 331, 974-980.
25. Hofmann, Y., and Wirth, B. (2002). hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-b1. Hum. Mol. Genet. 11, 2037-2049.
26. Lam, B.J., and Hertel, K.J. (2002). A general role for splicing enhancers in exon definition. RNA 8, 1233-1241.
27. Lewandowska, M.A., Stuani, C., Parvizpur, A., Baralle, F.E., and Pagani, F. (2005). Functional studies on the ATM intronic splicing processing element. Nucleic Acids Res. 33, 4007-4015.
28. Madden, H.R., Fletcher, S., Davis, M.R., and Wilton, S.D. (2009). 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. Mayeda, A., Screaton, G.R., Chandler, S.D., Fu, X.D., and Krainer, A.R. (1999). Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre-mRNA exonic elements. Mol. Cell. Biol. 19, 1853-1863.
30. Metherell, L.A., Akker, S.A., Munroe, P.B., Rose, S.J., Caulfield, M., Savage, M.O., Chew, S.L., and Clark, A.J. (2001). Pseu-doexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity. Am. J. Hum. Genet. 69, 641-646.
31. Muntoni, F., Melis, M.A., Ganau, A., and Dubowitz, V. (1995). Transcription of the dystrophin gene in normal tissues and in skeletal muscle of a family with X-linked dilated cardiomy-opathy. Am. J. Hum. Genet. 56, 151-157.
32. Muntoni, F., Torelli, S., and Ferlini, A. (2003). Dystrophin and mutations: One gene, several proteins, multiple phenotypes. Lancet Neurol. 2, 731-740.
33. Nasim, M.T., Chernova, T.K., Chowdhury, H.M., Yue, B.G., and Eperon, I.C. (2003). hnRNP G and Tra2b: Opposite effects on splicing matched by antagonism in RNA binding. Hum. Mol. Genet. 12, 1337-1348.
34. Pagani, F., Buratti, E., Stuani, C., Bendix, R., Dörk, T., and Baralle, F.E. (2002). A new type of mutation causes a splicing defect in ATM. Nat. Genet. 30, 426-429.
35. Qi, J., Su, S., McGuffin, M.E., and Mattox, W. (2006). Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing. Nucleic Acids Res. 34, 6256-6263.
36. Rimessi, P., Gualandi, F., Duprez, L., Spitali, P., Neri, M., Mer-lini, L., Calzolari, E., Muntoni, F., and Ferlini, A. (2005). Genomic and transcription studies as diagnostic tools for a prenatal detection of X-linked dilated cardiomyopathy due to a dystrophin gene mutation. Am. J. Med. Genet. A 132, 391-394.
37. Rimessi, P., Sabatelli, P., Fabris, M., Braghetta, P., Bassi, E., Spitali, P., Vattemi, G., Tomelleri, G., Mari, L., Perrone, D., Medici, A., Neri, M., Bovolenta, M., Martoni, E., Maraldi, N.M., Gualandi, F., Merlini, L., Balestri, M., Tondelli, L., Sparnacci, K., Bonaldo, P., Caputo, A., Laus, M., and Ferlini, A. (2009). Cationic PMMA nanoparticles bind and deliver antisense oligoribonucleotides allowing restoration of dystro-phin expression in the mdx mouse. Mol. Ther. 17, 820-827.
38. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY).
39. Sazani, P., and Kole, R. (2003). Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing. J. Clin. Invest. 112, 481-486.
40. Seth, P., Miller, H.B., Lasda, E.L., Pearson, J.L., and Garcia-Blanco, M.A. (2008). Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. J. Biol. Chem. 283, 10058-10067.
41. Singh, N.N., Androphy, E.J., and Singh, R.N. (2004). An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy. Biochem. Biophys. Res. Commun. 315, 381-388.
42. Smith, C.W., and Valcarcel, J. (2000). Alternative pre-mRNA splicing: The logic of combinatorial control. Trends Biochem. Sci. 25, 381-388.
43. Solis, A.S., Shariat, N., and Patton, J.G. (2008). Splicing fidelity, enhancers, and disease. Front. Biosci. 13, 1926-1942.
44. Tarn, W.Y. (2007). Cellular signals modulate alternative splicing. J. Biomed. Sci. 14, 517-522.
45. Tran, Q., Coleman, T.P., and Roesser, J.R. (2003). Human transformer 2b and SRp55 interact with a calcitonin-specific splice enhancer. Biochim. Biophys. Acta. 1625, 141-152.
46. Tuffery-Giraud, S., Saquet, C., Chambert, S., and Claustres, M. (2003). Pseudoexon activation in the DMD gene as a novel mechanism for Becker muscular dystrophy. Hum. Mutat. 21, 608-614.
47. Valcarcel, J., and Green, M.R. (1996). The SR protein family: Pleiotropic functions in pre-mRNA splicing. Trends Biochem. Sci. 21, 296-301.
48. 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. (Pubitemid 46965325)
49. Zheng, Z.M. (2004). Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression. J. Biomed. Sci. 11, 278-294.
50. Zhu, J., Mayeda, A., and Krainer, A.R. (2001). Exon identity established through differential antagonism between exonic splicing silencer bound hnRNP A1 and enhancer bound SR proteins. Mol. Cell. 8, 1351-1361.
51. Zuker, M. (2003). Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406-3415.