Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model

Genes and Development

Volumn 24, Issue 15, 2010, Pages 1634-1644

  Hua, Yimin ^a   Sahashi, Kentaro ^a   Hung, Gene ^b   Rigo, Frank ^b   Passini, Marco A ^c   Bennett, C Frank ^b   Krainer, Adrian R ^a  

^a Howard Hughes Medical Institute Cold Spring Harbor Laboratory Cold Spring Harbor   (United States)

^b ISIS PHARMACEUTICALS   (United States)

^c GENZYME CORPORATION   (United States)

Author keywords

Antisense oligonucleotide; Mouse models; SMN2; Spinal cord; Spinal muscular atrophy; Splicing correction

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; MESSENGER RNA; SURVIVAL MOTOR NEURON PROTEIN 2; SMN2 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTISENSE THERAPY; ARTICLE; CONTROLLED STUDY; DISEASE MODEL; DRUG MEGADOSE; EMBRYO; EXON; GENE EXPRESSION; INTRON; LATERAL BRAIN VENTRICLE; MOTONEURON; MOUSE; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROCESSING; SPINAL CORD; SPINAL MUSCULAR ATROPHY; TISSUE NECROSIS; TRANSGENE; ALTERNATIVE RNA SPLICING; ANIMAL; ANIMAL EMBRYO; DRUG EFFECT; FEMALE; GENE EXPRESSION REGULATION; GENETICS; MALE; METABOLISM; NECROSIS; PATHOPHYSIOLOGY;

MUS; MUS MUSCULUS;

ALTERNATIVE SPLICING; ANIMALS; ANIMALS, NEWBORN; DISEASE MODELS, ANIMAL; EMBRYO, MAMMALIAN; FEMALE; GENE EXPRESSION REGULATION; MALE; MICE; MOTOR NEURONS; MUSCULAR ATROPHY, SPINAL; NECROSIS; OLIGONUCLEOTIDES, ANTISENSE; SPINAL CORD; SURVIVAL OF MOTOR NEURON 2 PROTEIN; TRANSGENES;

EID: 77955894067     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1941310     Document Type: Article

References (58)

1. Allo M, Buggiano V, Fededa JP, Petrillo E, Schor I, de la Mata M, Agirre E, Plass M, Eyras E, Elela SA, et al. 2009. Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nat Struct Mol Biol 16: 717-724.
2. Arai H, Tanabe Y, Hachiya Y, Otsuka E, Kumada S, FurushimaW, Kohyama J, Yamashita S, Takanashi J, Kohno Y. 2005. Finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation in patients with progressive spinal muscular atrophy. J Child Neurol 20: 871-875. (Pubitemid 43125263)
3. Araujo Ade Q, Araujo M, Swoboda KJ. 2009. Vascular perfusion abnormalities in infants with spinal muscular atrophy. J Pediatr 155: 292-294.
4. Baker BF, Lot SS, Condon TP, Cheng-Flournoy S, Lesnik EA, Sasmor HM, Bennett CF. 1997. 29-O-(2-methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells. J Biol Chem 272: 11994-12000. (Pubitemid 27202775)
5. Baughan TD, Dickson A, Osman EY, Lorson CL. 2009. Delivery of bifunctional RNAs that target an intronic repressor and increase SMN levels in an animal model of spinal muscular atrophy. Hum Mol Genet 18: 1600-1611.
6. Belverud S, Mogilner A, Schulder M. 2008. Intrathecal pumps. Neurotherapeutics 5: 114-122.
7. Butler M, Stecker K, Bennett CF. 1997. Cellular distribution of phosphorothioate oligodeoxynucleotides in normal rodent tissues. Lab Invest 77: 379-388. (Pubitemid 27465599)
8. Butler M, Crooke RM, Graham MJ, Lemonidis KM, Lougheed M, Murray SF,Witchell D, Steinbrecher U, Bennett CF. 2000. Phosphorothioate oligodeoxynucleotides distribute similarly in class A scavenger receptor knockout and wild-type mice. J Pharmacol Exp Ther 292: 489-496. (Pubitemid 30067410)
9. Cartegni L, Krainer AR. 2003. Correction of disease-associated exon skipping by synthetic exon-specific activators. Nat Struct Biol 10: 120-125. (Pubitemid 36177092)
10. Coady TH, Lorson CL. 2010. Trans-splicing-mediated improvement in a severe mouse model of spinal muscular atrophy. J Neurosci 30: 126-130.
11. Coady TH, Shababi M, Tullis GE, Lorson CL. 2007. Restoration of SMN function: Delivery of a trans-splicing RNA re-directs SMN2 pre-mRNA splicing. Mol Ther 15: 1471-1478. (Pubitemid 47099304)
12. Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH. 1997. The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 6: 1205-1214. (Pubitemid 27351059)
13. Crawford TO. 2003. Spinal muscular atrophies. Butterworth-Heinemann, Philadelphia.
14. Crooke ST. 2004. Antisense strategies. Curr Mol Med 4: 465-487.
15. Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, et al. 2010. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol 28: 271-274.
16. Gabanella F, Butchbach ME, Saieva L, Carissimi C, Burghes AH, Pellizzoni L. 2007. Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS ONE 2: e921. doi: 10.1371/journal.pone.0000921. (Pubitemid 351472229)
17. Gavrilina TO, McGovern VL,Workman E, Crawford TO, Gogliotti RG, DiDonato CJ, Monani UR, Morris GE, Burghes AH. 2008. Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect. Hum Mol Genet 17: 1063-1075.
18. Geary RS, Yu RZ, Watanabe T, Henry SP, Hardee GE, Chappell A, Matson J, Sasmor H, Cummins L, Levin AA. 2003. Pharmacokinetics of a tumor necrosis factor-α phosphorothioate 2′-O-(2-methoxyethyl) modified antisense oligonucleotide: Comparison across species. Drug Metab Dispos 31: 1419-1428. (Pubitemid 37310332)
19. Geib T, Hertel KJ. 2009. Restoration of full-length SMN promoted by adenoviral vectors expressing RNA antisense oligonucleotides embedded in U7 snRNAs. PLoS ONE 4: e8204. doi: 10.1371/journal.pone.0008204.
20. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. 2010. Mechanisms underlying inflammation in neurodegeneration. Cell 140: 918-934.
21. Gogliotti RG, Hammond SM, Lutz C, Didonato CJ. 2010. Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy. Biochem Biophys Res Commun 391: 517-522.
22. Hsieh-Li HM, Chang JG, Jong YJ, Wu MH, Wang NM, Tsai CH, Li H. 2000. A mouse model for spinal muscular atrophy. Nat Genet 24: 66-70. (Pubitemid 30041423)
23. Hua Y, Vickers TA, Baker BF, Bennett CF, Krainer AR. 2007. Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon. PLoS Biol 5: e73. doi:10.1371/journal.pbio.0050073.
24. Hua Y, Vickers TA, Okunola HL, Bennett CF, Krainer AR. 2008. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet 82: 834-848.
25. Kolb SJ, Battle DJ, Dreyfuss G. 2007. Molecular functions of the SMN complex. J Child Neurol 22: 990-994.
26. Kumar P, Wu H, McBride JL, Jung KE, Kim MH, Davidson BL, Lee SK, Shankar P, Manjunath N. 2007. Transvascular delivery of small interfering RNA to the central nervous system. Nature 448: 39-43. (Pubitemid 47037001)
27. Le TT, Pham LT, Butchbach ME, Zhang HL, Monani UR, Coovert DD, Gavrilina TO, Xing L, Bassell GJ, Burghes AH. 2005. SMND7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14: 845-857. (Pubitemid 40403280)
28. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. 1995. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80: 155-165.
29. Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J. 1997. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16: 265-269. (Pubitemid 27280210)
30. Lim SR, Hertel KJ. 2001. Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3′ splice site pairing. J Biol Chem 276: 45476-45483. (Pubitemid 37391346)
31. Lima WF, Wu H, Nichols JG, Sun H, Murray HM, Crooke ST. 2009. Binding and cleavage specificities of human Argonaute2. J Biol Chem 284: 26017-26028.
32. Liu Q, Dreyfuss G. 1996. A novel nuclear structure containing the survival of motor neurons protein. EMBO J 15: 3555-3565. (Pubitemid 26239768)
33. Lunn MR, Wang CH. 2008. Spinal muscular atrophy. Lancet 371: 2120-2133.
34. Madocsai C, Lim SR, Geib T, Lam BJ, Hertel KJ. 2005. Correction of SMN2 pre-mRNA splicing by antisense U7 small nuclear RNAs. Mol Ther 12: 1013-1022. (Pubitemid 41723035)
35. McWhorter ML, Monani UR, Burghes AH, Beattie CE. 2003. Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. J Cell Biol 162: 919-931.
36. Meister G, Buhler D, Pillai R, Lottspeich F, Fischer U. 2001. A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nat Cell Biol 3: 945-949. (Pubitemid 34428738)
37. Meyer K, Marquis J, Trub J, Nlend Nlend R, Verp S, Ruepp MD, Imboden H, Barde I, Trono D, Schumperli D. 2009. Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicingmodulation. Hum Mol Genet 18: 546-555.
38. Miyajima H, Miyaso H, Okumura M, Kurisu J, Imaizumi K. 2002. Identification of a cis-acting element for the regulation of SMN exon 7 splicing. J Biol Chem 277: 23271-23277. (Pubitemid 34952155)
39. -/- mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9: 333-339.
40. Munsat TL, Davies KE. 1992. International SMA consortium meeting. (26-28 June 1992, Bonn, Germany). Neuromuscul Disord 2: 423-428.
41. Narver HL, Kong L, Burnett BG, Choe DW, Bosch-Marce M, Taye AA, Eckhaus MA, Sumner CJ. 2008. Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol 64: 465-470.
42. Passini MA, Bu J, Roskelley EM, Richards AM, Sardi SP, O'Riordan CR, Klinger KW, Shihabuddin LS, Cheng SH. 2010. CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy. J Clin Invest 120: 1253-1264.
43. Pellizzoni L, Yong J, Dreyfuss G. 2002. Essential role for the SMN complex in the specificity of snRNP assembly. Science 298: 1775-1779. (Pubitemid 35404118)
44. Riessland M, Ackermann B, Forster A, Jakubik M, Hauke J, Garbes L, Fritzsche I, Mende Y, Blumcke I, Hahnen E, et al. 2010. SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy. Hum Mol Genet 19: 1492-1506.
45. Russman BS. 2007. Spinal muscular atrophy: Clinical classification and disease heterogeneity. J Child Neurol 22: 946-951. (Pubitemid 47308307)
46. Saito T. 2006. In vivo electroporation in the embryonic mouse central nervous system. Nat Protoc 1: 1552-1558.
47. Schrank B, Gotz R, Gunnersen JM, Ure JM, Toyka KV, Smith AG, Sendtner M. 1997. Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci 94: 9920-9925. (Pubitemid 27408166)
48. Singh NK, Singh NN, Androphy EJ, Singh RN. 2006. Splicing of a critical exon of human survival motor neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol 26: 1333-1346.
49. Skordis LA, Dunckley MG, Yue B, Eperon IC, Muntoni F. 2003. Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts. Proc Natl Acad Sci 100: 4114-4119. (Pubitemid 36418166)
50. Smith RA, Miller TM, Yamanaka K, Monia BP, Condon TP, Hung G, Lobsiger CS, Ward CM, McAlonis-Downes M, Wei H, et al. 2006. Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest 116: 2290-2296. (Pubitemid 44162339)
51. Tsai LK, Tsai MS, Lin TB, Hwu WL, Li H. 2006. Establishing a standardized therapeutic testing protocol for spinal muscular atrophy. Neurobiol Dis 24: 286-295. (Pubitemid 44572748)
52. Tsai LK, Tsai MS, Ting CH, Li H. 2008. Multiple therapeutic effects of valproic acid in spinal muscular atrophy model mice. J Mol Med 86: 1243-1254.
53. Vinogradov SV, Batrakova EV, Kabanov AV. 2004. Nanogels for oligonucleotide delivery to the brain. Bioconjug Chem 15: 50-60.
54. Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A, Wong B, Aloysius A, Morrison L, Main M, Crawford TO, et al. 2007. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 22: 1027-1049. (Pubitemid 47308318)
55. Whitesell L, Geselowitz D, Chavany C, Fahmy B, Walbridge S, Alger JR, Neckers LM. 1993. Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: Implications for therapeutic application within the central nervous system. Proc Natl Acad Sci 90: 4665-4669. (Pubitemid 23148966)
56. Williams JH, Schray RC, Patterson CA, Ayitey SO, Tallent MK, Lutz GJ. 2009. Oligonucleotide-mediated survival of motor neuron protein expression in CNS improves phenotype in a mouse model of spinal muscular atrophy. J Neurosci 29: 7633-7638.
57. Yang ZF, Ho DW, Lau CK, Lam CT, Lum CT, Poon RT, Fan ST. 2005. Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int Immunol 17: 1391-1397.
58. Zhang H, Xing L, Rossoll W, Wichterle H, Singer RH, Bassell GJ. 2006.Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. J Neurosci 26: 8622-8632. (Pubitemid 44316191)