Peptide conjugation of 2′-O-methyl phosphorothioate antisense oligonucleotides enhances cardiac uptake and exon skipping in mdx mice

Nucleic Acid Therapeutics

Volumn 24, Issue 1, 2014, Pages 25-36

  Jirka, Silvana M G ^a   Heemskerk, Hans ^a   Tanganyika De Winter, Christa L ^a   Muilwijk, Daan ^b   Pang, Kar Him ^b   De Visser, Peter C ^b   Janson, Anneke ^b   Karnaoukh, Tatyana G ^b   Vermue, Rick ^b   'T Hoen, Peter A C ^a   Van Deutekom, Judith C T ^b   Aguilera, Begoña ^b   Aartsma Rus, Annemieke ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b Prosensa Therapeutics BV   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

2 O METHYL PHOSPHOROTHIONATE; ANTISENSE OLIGONUCLEOTIDE; CELL PENETRATING PEPTIDE; DYSTROPHIN; MORPHOLINO OLIGONUCLEOTIDE; PHOSPHOROTHIOIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BECKER MUSCULAR DYSTROPHY; BIOPANNING; CLINICAL TRIAL (TOPIC); CONJUGATION; CONTROLLED STUDY; DUCHENNE MUSCULAR DYSTROPHY; EXON SKIPPING; GASTROCNEMIUS MUSCLE; HEART MUSCLE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; MUSCLE CELL; MYOTUBE; NONHUMAN; OPEN READING FRAME; PEPTIDE LIBRARY; PEPTIDE SYNTHESIS; PHAGE DISPLAY; PRIORITY JOURNAL; THERAPY EFFECT; X CHROMOSOME LINKED MUSCULAR DYSTROPHIC MOUSE;

ANIMALS; DYSTROPHIN; EXONS; HUMANS; MALE; MICE; MICE, INBRED MDX; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, ANIMAL; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION; MYOCARDIUM; OLIGONUCLEOTIDES, ANTISENSE; PEPTIDE LIBRARY; PEPTIDE NUCLEIC ACIDS; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; TARGETED GENE REPAIR;

EID: 84893589833     PISSN: 21593337     EISSN: None     Source Type: Journal    
DOI: 10.1089/nat.2013.0448     Document Type: Article

References (35)

1. AARTSMA-RUS, A. (2010). Antisense-mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy. RNA Biol. 7, 453-461.
2. AARTSMA-RUS, A., JANSON, A.A., KAMAN,W.E., BREMMERBOUT, M., DEN DUNNEN, J.T., BAAS, F., VAN OMMEN G.J., and VAN DEUTEKOM J.C. (2003). Therapeutic antisenseinduced exon skipping in cultured muscle cells from six different DMD patients. Hum Mol Genet 12, 907-914.
3. 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.
4. EMMER-BOUT, M., AARTSMA-RUS, A., DE MEIJER, E.J., KAMAN, W.E., JANSON, A.A., VOSSEN, R.H., VAN OMMEN, G.J., DEN DUNNEN, J.T., and VAN DEUTENKOM, J.C. (2004). Targeted exon skipping in transgenic hDMD mice: a model for direct preclinical screening of human-specific antisense oligonucleotides. Mol. Ther. 10, 232-240.
5. CIRAK, S., ARECHAVALA-GOMEZA, V., GUGLIERI, M., FENG, L., TORELLI, S., ANTHONY, K., ABBS, S., GARRALDA, M.E., BOURKE, J., WELLS, D.J., DICKSON, G., et al. (2011). Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an openlabel, phase 2, dose-escalation study. Lancet 378, 595-605.
6. EMERY, A.E. (2002). The muscular dystrophies. Lancet 359, 687-695.
7. FLETCHER, S., HONEYMAN, K., FALL, A.M., HARDING, 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.
8. 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. et al. (2011). Systemic administration of PRO051 in Duchenne's muscular dystrophy. N. Engl. J. Med. 364, 1513-1522.
9. 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., AARSTMA-RUS, A. et al. (2010). Preclinical PK and PD studies on 2¢-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol. Ther. 18, 1210-1217.
10. HEEMSKERK, H.A., DE WINTER, C.L., DE KIMPE, S.J., VAN KUIK-ROMEIJN, P., HEUVELMANS, N., PLATENBURG, G.J., VANOMMEN,G.J., DEUTENKOM, J.C., andAARTSMA-RUS, A. (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.
11. HUANG, J., RU, B., LI, S., LIN, H., and GUO, F.B. (2010). SAROTUP: scanner and reporter of target-unrelated peptides. J. Biomed. Biotechnol. 2010, 101932.
12. JULIANO, R.L., MING, X., and NAKAGAWA, O. (2012). Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides. Bioconjug. Chem. 23, 147-157.
13. KEHOE, J.W., and KAY, B.K. (2005). Filamentous phage display in the new millennium. Chem. Rev. 105, 4056-4072.
14. MALERBA, A., BOLDRIN, L., and DICKSON, G. (2011). Longterm 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.
15. MANN, C.J., HONEYMAN, K., MCCLOREY, G., FLETCHER, S., and WILTON, S.D. (2002). Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy. J. Gene Med. 4, 644-654.
16. MCCLOREY, G., MOULTON, H.M., IVERSEN, P.L., FLETCHER, S., and WILTON, S.D. (2006). Antisense oligonucleotideinduced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther. 13, 1373-1381.
17. MOAT, S.J., BRADLEY, D.M., SALMON, R., CLARKE, A., and HARTLEY, L. (2013). Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK). Eur. J. Hum. Genet. 21, 1049-1053.
18. MONACO, A.P., BERTELSON, C.J., LIECHTI-GALLATI, S., MOSER, H., and KUNKEL, L.M. (1988). An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2, 90-95.
19. MOULTON, H.M., WU, B., JEARAWIRIYAPAISARN, N., SAZANI, P., LU, Q.L., and KOLE, R. (2009). Peptide-morpholino conjugate: a promising therapeutic for Duchenne muscular dystrophy. Ann. N. Y. Acad. Sci. 1175, 55-60.
20. 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.
21. MUNTONI, F., TORELLI, S., and FERLINI, A. (2003). Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2, 731-740.
22. SAMOYLOVA, T.I., and SMITH, B.F. (1999). Elucidation of muscle-binding peptides by phage display screening. Muscle Nerve 22, 460-466.
23. SCOTT, J.K., and SMITH, G.P. (1990). Searching for peptide ligands with an epitope library. Science 249, 386-390.
24. SEOW, Y., YIN, H., and WOOD, M.J. (2010). Identification of a novel muscle targeting peptide in mdx mice. Peptides 31, 1873-1877.
25. SHTATLAND, T., GUETTLER, D., KOSSODO,M., PIVOVAROV, M., and WEISSLEDER, R. (2007). PepBank-a database of peptides based on sequence text mining and public peptide data sources. BMC Bioinformatics 8, 280.
26. THOEN, P.A., JIRKA, S.M., TEN BROEKE, B.R., SCHULTES, E.A., AGUILERA, B., PANG, K.H., HEEMSKERK, H., AARTSMA-RUS, A., VAN OMMEN, G.J., and DEN DUNNEN, J.T. et al. (2012). Phage display screening without repetitious selection rounds. Anal. Biochem. 421, 622-631.
27. TOWNSEND, D., YASUDA, S., CHAMBERLAIN, J., and METZGER, J.M. (2009). Cardiac consequences to skeletal muscle-centric therapeutics for Duchenne muscular dystrophy. Trends Cardiovasc. Med. 19, 50-55.
28. VAN PUTTENM., and AARTSMA-RUS, A. (2011). Opportunities and challenges for the development of antisense treatment in neuromuscular disorders. ExpertOpin. Biol. Ther. 11, 1025-1037.
29. VERHAART, I.E., TANGANYIKA-DE WINTER, C.L., KARNAOUKH, T.G., KOLFSCHOTEN, I.G., DE KIMPE, S.J., VAN DEUTEKOM, J.C., and AARTSMA-RUS, A. (2013). Dose-dependent pharmacokinetic profiles of 2¢-O-methyl phosphorothioate antisense oligonucleotidesin mdx mice. Nucleic Acid Ther. 23, 228-237.
30. WU, B., LU, P., CLOER, C., SHABAN,M., GREWAL, S., MILAZI, S., SHAH, S.N., MOULTON, H.M., and LI, Q.L. (2012). Longterm 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.
31. 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.
32. 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. (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.
33. YOKOTA, T., LU, Q.L., PARTRIDGE, T., KOBAYASHI, M., NAKAMURA, A., TAKEDA, S., and HOFFMAAN, E. (2009). Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann. Neurol. 65, 667-676.
34. YU, R.Z., BAKER, B., CHAPPELL, A., GEARY, R.S., CHEUNG, E., and LEVIN, A.A. (2002). Development of an ultrasensitive noncompetitive hybridization-ligation enzyme-linked immunosorbent assay for the determination of phosphorothioate oligodeoxynucleotide in plasma. Anal. Biochem. 304, 19-25.
35. ZAHID, M., PHILLIPS, B.E., ALBERS, S.M., GIANNOUKAKIS, N., WATKINS, S.C., and ROBBINS, P.D. (2010). Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice. PLoS One 5, e12252.