Antisense-mediated exon skipping: Taking advantage of a trick from Mother Nature to treat rare genetic diseases

Experimental Cell Research

Volumn 325, Issue 1, 2014, Pages 50-55

  Veltrop, Marcel ^a   Aartsma Rus, Annemieke ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Antisense oligonucleotides; Exon skipping; Rare disease; Splicing

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; BONE MORPHOGENETIC PROTEIN; CELL PENETRATING PEPTIDE; CEP290 PROTEIN; DYSTROPHIN; MICROTUBULE ASSOCIATED PROTEIN; MYOSTATIN; PROTEIN; RYANODINE RECEPTOR; SURVIVAL MOTOR NEURON PROTEIN 2; TAU PROTEIN; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; AUTOSOMAL DOMINANT DISORDER; BECKER MUSCULAR DYSTROPHY; BLINDNESS; CELL DIFFERENTIATION; CELL TRANSDIFFERENTIATION; CHROMOSOME 17; DISABILITY SEVERITY; DISEASE COURSE; DISEASE SEVERITY; DUCHENNE MUSCULAR DYSTROPHY; EXON SKIPPING; GENE EXPRESSION; GENE MUTATION; GENE SILENCING; GENETIC DISORDER; GROWTH INHIBITION; HUMAN; LEBER CONGENITAL AMAUROSIS; LIFE EXPECTANCY; MUSCLE GROWTH; NATURAL SCIENCE; NONHUMAN; OPEN READING FRAME; OSSIFICATION; OSSIFYING MYOSITIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN FUNCTION; RARE DISEASE; RETINA DEGENERATION; REVIEW; SPINAL MUSCULAR ATROPHY; TARGET ORGAN; TAUOPATHY;

ANTISENSE OLIGONUCLEOTIDES; EXON SKIPPING; RARE DISEASE; SPLICING;

ANIMALS; EXONS; GENE KNOCKDOWN TECHNIQUES; HUMANS; LEBER CONGENITAL AMAUROSIS; MUSCULAR ATROPHY, SPINAL; MUSCULAR DYSTROPHY, DUCHENNE; MYOSITIS OSSIFICANS; OLIGONUCLEOTIDES, ANTISENSE; RNA INTERFERENCE; RNA SPLICING; TAUOPATHIES;

EID: 84901830311     PISSN: 00144827     EISSN: 10902422     Source Type: Journal    
DOI: 10.1016/j.yexcr.2014.01.026     Document Type: Review

References (46)

1. Aartsma-Rus A., den Dunnen J.T., van Ommen G.J. New insights in gene-derived therapy: the example of Duchenne muscular dystrophy. Ann. N. Y. Acad. Sci 2010, 1214:199-212.
2. Aartsma-Rus A., Fokkema I., Verschuuren J., Ginjaar I., van Deutekom J., van Ommen G.J., den Dunnen J.T. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum. Mutat. 2009, 3:257-266.
3. Amthor H., Macharia R., Navarrete R., Schuelke M., Brown S.C., Otto A., Voit T., Muntoni F., Vrbova G., Partridge T., Zammit P., Bunger L., Patel K. Lack of myostatin results in excessive muscle growth but impaired force generation. Proc. Nat. Acad. Sci. U.S.A 2007, 104:1835-1840.
4. Aoki Y., Yokota T., Wood M.J. Development of multiexon skipping antisense oligonucleotide therapy for Duchenne muscular dystrophy. Biomed. Res. Int 2013, (2013).
5. Betts C., Saleh A.F., Arzumanov A.A., Hammond S.M., Godfrey C., Coursindel T., Gait M.J., Wood M.J. Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment. Mol. Ther. Nucleic Acids 2012, 1:e38.
6. Chang B., Khanna H., Hawes N., Jimeno D., He S., Lillo C., Parapuram S.K., Cheng H., Scott A., Hurd R.E., Sayer J.A., Otto E.A., Attanasio M., O'Toole J.F., Jin G., Shou C., Hildebrandt F., Williams D.S., Heckenlively J.R., Swaroop A. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum. Mol. Genet. 2006, 15:1847-1857.
7. 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., Wood M.J., Wilton S.D., Straub V., Kole R., Shrewsbury S.B., Sewry C., Morgan J.E., Bushby K., Muntoni F. 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 2011, 378:595-605.
8. Collin R.W., den Hollander A.I., van der Velde-Visser S.D., Bennicelli J., Bennett J., Cremers F.P. Antisense oligonucleotide (AON)-based therapy for Leber congenital amaurosis caused by a frequent mutation in CEP290. Mol. Ther. Nucleic Acids 2012, 1:e14.
9. D'Amico A., Mercuri E., Tiziano F.D., Bertini E. Spinal muscular atrophy. Orphanet. J. Rare Dis. 2011, 6:71.
10. Douglas A.G., Wood M.J. Splicing therapy for neuromuscular disease. Mol. Cell Neurosci. 2013, 56:169-185.
11. Drivas T.G., Holzbaur E.L., Bennett J. Disruption of CEP290 microtubule/membrane-binding domains causes retinal degeneration. J. Clin. Invest. 2013, 123:4525-4539.
12. Gerard X., Perrault I., Hanein S., Silva E., Bigot K., Defoort-Delhemmes S., Rio M., Munnich A., Scherman D., Kaplan J., Kichler A., Rozet J.M. AON-mediated exon skipping restores ciliation in fibroblasts harboring the common Leber congenital amaurosis CEP290 mutation. Mol. Ther. Nucleic Acids 2012, 1:e29.
13. Giannesini B., Vilmen C., Amthor H., Bernard M., Bendahan D. Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo. Am. J. Physiol. Endocrinol. Metab. 2013, 305:E33-E40.
14. 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., Darin N., Verschuuren J.J., Campion G.V., de Kimpe S.J., van Deutekom J.C. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N. Engl. J. Med. 2011, 364:1513-1522.
15. Goyenvalle A., Vulin A., Fougerousse F., Leturcq F., Kaplan J.C., Garcia L., Danos O. Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 2004, 306:1796-1799.
16. Gumucio A., Lannfelt L., Nilsson L.N. Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging. BMC Neurosci 2013, 14:148.
17. Havens M.A., Duelli D.M., Hastings M.L. Targeting RNA splicing for disease therapy. Wiley Interdiscip. Rev. RNA 2013, 4:247-266.
18. Heemskerk H., de W.C., van K.P., Heuvelmans N., Sabatelli P., Rimessi P., Braghetta P., van Ommen G.J., de K.S., Ferlini A., Aartsma-Rus A., van Deutekom J.C. Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol. Ther. 2010, 18:1210-1217.
19. Hua Y., Sahashi K., Rigo F., Hung G., Horev G., Bennett C.F., Krainer A.R. Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature 2011, 478:123-126.
20. Jarver P., O'Donovan L., Gait M.J. A chemical view of oligonucleotides for exon skipping and related drug applications. Nucleic Acid Ther 2013.
21. Kang J.K., Malerba A., Popplewell L., Foster K., Dickson G. Antisense-induced myostatin exon skipping leads to muscle hypertrophy in mice following octa-guanidine morpholino oligomer treatment. Mol. Ther 2011, 19:159-164.
22. Kaplan F.S., Chakkalakal S.A., Shore E.M. Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Dis. Model. Mech 2012, 5:756-762.
23. Kemaladewi D.U., Hoogaars W.M., van Heiningen S.H., Terlouw S., de Gorter D.J., den Dunnen J.T., van Ommen G.J., artsma-Rus A., ten D.P., 't Hoen P.A. Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy. BMC Med. Genomics 2011, 4:36.
24. Kinali M., Arechavala-Gomeza V., Feng L., Cirak S., Hunt D., Adkin C., Guglieri M., Ashton E., Abbs S., Nihoyannopoulos P., Garralda M.E., Rutherford M., McCulley C., Popplewell L., Graham I.R., Dickson G., Wood M.J., Wells D.J., Wilton S.D., Kole R., Straub V., Bushby K., Sewry C., Morgan J.E., Muntoni F. 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. 2009, 8:918-928.
25. Koo T., Wood M.J. Clinical trials using antisense oligonucleotides in duchenne muscular dystrophy. Hum. Gene Ther 2013, 24:479-488.
26. Lu Q.L., Mann C.J., Lou F., Bou-Gharios G., Morris G.E., Xue S.A., Fletcher S., Partridge T.A., Wilton S.D. Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat. Med 2003, 9:1009-1014.
27. Malerba A., Kang J.K., McClorey G., Saleh A.F., Popplewell L., Gait M.J., Wood M.J., Dickson G. Dual myostatin and dystrophin exon skipping by morpholino nucleic acid oligomers conjugated to a cell-penetrating peptide is a promising therapeutic strategy for the treatment of Duchenne muscular dystrophy. Mol. Ther. Nucleic Acids 2012, 1:e62.
28. R. Mendell, L.R. Rodino-Klapac, Z. Sahenk, K. Roush, L. Bird, L.P. Lowes, L. Alfano, A.M. Gomez, S. Lewis, J. Kota, V. Malik, K. Shontz, C.M. Walker, K.M. Flanigan, M. Corridore, J.R. Kean, H.D. Allen, C. Shilling, K.R. Melia, P. Sazani, J.B. Saoud, E.M. Kaye, Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann. Neurol.2013).
29. Mesfin A., Sponseller P.D., Leet A.I. Spinal muscular atrophy: manifestations and management. J. Am. Acad. Orthop. Surg. 2012, 20:393-401.
30. Miao J., Zhang C., Wu S., Peng Z., Tania M. Genetic abnormalities in fibrodysplasia ossificans progressiva. Genes Genet. Syst. 2012, 87:213-219.
31. Miller T.M., Pestronk A., David W., Rothstein J., Simpson E., Appel S.H., Andres P.L., Mahoney K., Allred P., Alexander K., Ostrow L.W., Schoenfeld D., Macklin E.A., Norris D.A., Manousakis G., Crisp M., Smith R., Bennett C.F., Bishop K.M., Cudkowicz M.E. 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. 2013, 12:435-442.
32. Mitrpant C., Porensky P., Zhou H., Price L., Muntoni F., Fletcher S., Wilton S.D., Burghes A.H. Improved antisense oligonucleotide design to suppress aberrant SMN2 gene transcript processing: towards a treatment for spinal muscular atrophy. PLoS One 2013, 8:e62114.
33. Narfstrom K., Holland D.K., Menotti-Raymond M. The domestic cat as a large animal model for characterization of disease and therapeutic intervention in hereditary retinal blindness. J. Ophthalmol 2011, 2011:906943.
34. Niblock M., Gallo J.M. Tau alternative splicing in familial and sporadic tauopathies. Biochem. Soc. Trans. 2012, 40:677-680.
35. Peacey E., Rodriguez L., Liu Y., Wolfe M.S. Targeting a pre-mRNA structure with bipartite antisense molecules modulates tau alternative splicing. Nucleic Acids Res 2012, 40:9836-9849.
36. Porensky P.N., Burghes A.H. Antisense oligonucleotides for the treatment of spinal muscular atrophy. Hum. Gene Ther 2013, 24:489-498.
37. Rendu J., Brocard J., Denarier E., Monnier N., Pietri-Rouxel F., Beley C., Roux-Buisson N., Gilbert-Dussardier B., Perez M.J., Romero N., Garcia L., Lunardi J., Faure J., Fourest-Lieuvin A., Marty I. Exon skipping as a therapeutic strategy applied to an RYR1 mutation with pseudo-exon inclusion causing a severe core myopathy. Hum. Gene Ther. 2013, 24:702-713.
38. Shi S., Cai J., de Gorter D.J., Sanchez-Duffhues G., Kemaladewi D.U., Hoogaars W.M., Aartsma-Rus A., 't Hoen P.A., ten D.P. Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva. PLoS One 2013, 8:e69096.
39. Shiraishi T., Nielsen P.E. Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers. Artif. DNA PNA XNA 2011, 2:90-99.
40. Spitali P., Aartsma-Rus A. Splice modulating therapies for human disease. Cell 2012, 148:1085-1088.
41. Umeda T., Yamashita T., Kimura T., Ohnishi K., Takuma H., Ozeki T., Takashima A., Tomiyama T., Mori H. 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 2013, 183:211-225.
42. van den Bergen J.C., Schade van Westrum S.M., Dekker L., van der Kooi A.J., de V.M., Wokke B.H., Straathof C.S., Hulsker M.A., Aartsma-Rus A., Verschuuren J.J., Ginjaar H.B. Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy. J. Neurol. Neurosurg. Psychiatry 2013.
43. van Deutekom J.C., Janson A.A., Ginjaar I.B., Frankhuizen W.S., Aartsma-Rus A., Bremmer-Bout M., den Dunnen J.T., Koop K., van der Kooi A.J., Goemans N.M., de Kimpe S.J., Ekhart P.F., Venneker E.H., Platenburg G.J., Verschuuren J.J., van Ommen G.J. Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 2007, 357:2677-2686.
44. Zhang L., Li X., Zhao R. Structural analyses of the pre-mRNA splicing machinery. Protein Sci 2013, 22:677-692.
45. Zhou H., Janghra N., Mitrpant C., Dickinson R.L., Anthony K., Price L., Eperon I.C., Wilton S.D., Morgan J., Muntoni F. A novel morpholino oligomer targeting ISS-N1 improves rescue of severe spinal muscular atrophy transgenic mice. Hum. Gene Ther. 2013, 24:331-342.
46. H.L. Zhou, G. Luo, J.A. Wise, H. Lou, Regulation of alternative splicing by local histone modifications: potential roles for RNA-guided mechanisms. Nucleic Acids Res.2013).