1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genomics and Human Genetics
  4. Volume 15, 2014
  5. Article

Annual Review of Genomics and Human Genetics

Volume 15, 2014

Therapeutics Based on Stop Codon Readthrough

Abstract

Nonsense suppression therapy encompasses approaches aimed at suppressing translation termination at in-frame premature termination codons (PTCs, also known as nonsense mutations) to restore deficient protein function. In this review, we examine the current status of PTC suppression as a therapy for genetic diseases caused by nonsense mutations. We discuss what is currently known about the mechanism of PTC suppression as well as therapeutic approaches under development to suppress PTCs. The approaches considered include readthrough drugs, suppressor tRNAs, PTC pseudouridylation, and inhibition of nonsense-mediated mRNA decay. We also discuss the barriers that currently limit the clinical application of nonsense suppression therapy and suggest how some of these difficulties may be overcome. Finally, we consider how PTC suppression may play a role in the clinical treatment of genetic diseases caused by nonsense mutations.

Keyword(s): nonsense mutation, nonsense suppression therapy, premature termination codons, readthrough
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-091212-153527
2014-08-31
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/genom/15/1/annurev-genom-091212-153527.html?itemId=/content/journals/10.1146/annurev-genom-091212-153527&mimeType=html&fmt=ahah

Literature Cited

  1. Ali BH, Al Za'abi M, Blunden G, Nemmar A. 1.  2011. Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research. Basic Clin. Pharmacol. Toxicol. 109:225–32 [Google Scholar]
  2. Alkalaeva EZ, Pisarev AV, Frolova LY, Kisselev LL, Pestova TV. 2.  2006. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell 125:1125–36 [Google Scholar]
  3. Allamand V, Bidou L, Arakawa M, Floquet C, Shiozuka M. 3.  et al. 2008. Drug-induced readthrough of premature stop codons leads to the stabilization of laminin α2 chain mRNA in CMD myotubes. J. Gene Med. 10:217–24 [Google Scholar]
  4. Amrani N, Ganesan R, Kervestin S, Mangus DA, Ghosh S, Jacobson A. 4.  2004. A faux 3′-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Nature 432:112–18 [Google Scholar]
  5. Arakawa M, Nakayama Y, Hara T, Shiozuka M, Takeda S. 5.  et al. 2001. Negamycin can restore dystrophin in mdx skeletal muscle. Acta Myol. 20:154–58 [Google Scholar]
  6. Arakawa M, Shiozuka M, Nakayama Y, Hara T, Hamada M. 6.  et al. 2003. Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice. J. Biochem. 134:751–58 [Google Scholar]
  7. Auld DS, Lovell S, Thorne N, Lea WA, Maloney DJ. 7.  et al. 2010. Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124. Proc. Natl. Acad. Sci. USA 107:4878–83 [Google Scholar]
  8. Auld DS, Thorne N, Maguire WF, Inglese J. 8.  2009. Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression. Proc. Natl. Acad. Sci. USA 106:3585–90 [Google Scholar]
  9. Bartolomeo R, Polishchuk EV, Volpi N, Polishchuk RS, Auricchio A. 9.  2013. Pharmacological read-through of nonsense ARSB mutations as a potential therapeutic approach for mucopolysaccharidosis VI. J. Inherit. Metab. Dis. 36:363–71 [Google Scholar]
  10. Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL. 10.  1999. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J. Clin. Investig. 104:375–81 [Google Scholar]
  11. Bell J. 11.  2005. Amlexanox for the treatment of recurrent aphthous ulcers. Clin. Drug Investig. 25:555–66 [Google Scholar]
  12. Bhuvanagiri M, Schlitter AM, Hentze MW, Kulozik AE. 12.  2010. NMD: RNA biology meets human genetic medicine. Biochem. J. 430:365–77 [Google Scholar]
  13. Brendel C, Belakhov V, Werner H, Wegener E, Gartner J. 13.  et al. 2010. Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model. J. Mol. Med. 89:389–98 [Google Scholar]
  14. Brumm H, Muhlhaus J, Bolze F, Scherag S, Hinney A. 14.  et al. 2012. Rescue of melanocortin 4 receptor (MC4R) nonsense mutations by aminoglycoside-mediated read-through. Obesity 20:1074–81 [Google Scholar]
  15. Buck NE, Wood LR, Hamilton NJ, Bennett MJ, Peters HL. 15.  2012. Treatment of a methylmalonyl-CoA mutase stopcodon mutation. Biochem. Biophys. Res. Commun. 427:753–57 [Google Scholar]
  16. Bunge S, Clements PR, Byers S, Kleijer WJ, Brooks DA, Hopwood JJ. 16.  1998. Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochim. Biophys. Acta 1407:249–56 [Google Scholar]
  17. Buvoli M, Buvoli A, Leinwand LA. 17.  2000. Suppression of nonsense mutations in cell culture and mice by multimerized suppressor tRNA genes. Mol. Cell. Biol. 20:3116–24 [Google Scholar]
  18. Campbell KC, Meech RP, Klemens JJ, Gerberi MT, Dyrstad SS. 18.  et al. 2007. Prevention of noise- and drug-induced hearing loss with d-methionine. Hear. Res. 226:92–103 [Google Scholar]
  19. Cassan M, Rousset JP. 19.  2001. UAG readthrough in mammalian cells: effect of upstream and downstream stop codon contexts reveal different signals. BMC Mol. Biol. 2:3 [Google Scholar]
  20. Chamberlain J. 20.  1997. Dystrophin levels required for genetic correction of Duchenne muscular dystrophy. Basic Appl. Myol. 7:251–55 [Google Scholar]
  21. Chan WK, Huang L, Gudikote JP, Chang YF, Imam JS. 21.  et al. 2007. An alternative branch of the nonsense-mediated decay pathway. EMBO J. 26:1820–30 [Google Scholar]
  22. Chang CW, Hui Y, Elchert B, Wang J, Li J, Rai R. 22.  2002. Pyranmycins, a novel class of aminoglycosides with improved acid stability: the SAR of d-pyranoses on ring III of pyranmycin. Org. Lett. 4:4603–6 [Google Scholar]
  23. Chavatte L, Kervestin S, Favre A, Jean-Jean O. 23.  2003. Stop codon selection in eukaryotic translation termination: comparison of the discriminating potential between human and ciliate eRF1s. EMBO J. 22:1644–53 [Google Scholar]
  24. Chen C-YA, Shyu A-B. 24.  2011. Mechanisms of deadenylation-dependent decay. Wiley Interdiscip. Rev. RNA 2:167–83 [Google Scholar]
  25. Clancy JP, Bebok Z, Ruiz F, King C, Jones J. 25.  et al. 2001. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 163:1683–92 [Google Scholar]
  26. Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S. 26.  et al. 2013. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax 68:818–25 [Google Scholar]
  27. Cosson B, Couturier A, Chabelskaya S, Kiktev D, Inge-Vechtomov S. 27.  et al. 2002. Poly(A)-binding protein acts in translation termination via eukaryotic release factor 3 interaction and does not influence [PSI+] propagation. Mol. Cell. Biol. 22:3301–15 [Google Scholar]
  28. Davidson DJ, Rolfe M. 28.  2001. Mouse models of cystic fibrosis. Trends Genet. 17:S29–37 [Google Scholar]
  29. Drake KM, Dunmore BJ, McNelly LN, Morrell NW, Aldred MA. 29.  2013. Correction of nonsense BMPR2 and SMAD9 mutations by ataluren in pulmonary arterial hypertension. Am. J. Respir. Cell Mol. Biol. 49:403–9 [Google Scholar]
  30. Dranchak PK, Di Pietro E, Snowden A, Oesch N, Braverman NE. 30.  et al. 2011. Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. J. Cell. Biochem. 112:1250–58 [Google Scholar]
  31. Du L, Damoiseaux R, Nahas S, Gao K, Hu H. 31.  et al. 2009. Nonaminoglycoside compounds induce readthrough of nonsense mutations. J. Exp. Med. 206:2285–97 [Google Scholar]
  32. Du L, Jung ME, Damoiseaux R, Completo G, Fike F. 32.  et al. 2013. A new series of novel small molecular weight compounds induce readthrough of all three types of nonsense mutations in the ATM gene. Mol. Ther. 21:1653–60 [Google Scholar]
  33. Du M, Jones JR, Lanier J, Keeling KM, Lindsey JR. 33.  et al. 2002. Aminoglycoside suppression of a premature stop mutation in a Cftr−/− mouse carrying a human CFTR-G542X transgene. J. Mol. Med. 80:595–604 [Google Scholar]
  34. Du M, Keeling KM, Fan L, Liu X, Bedwell DM. 34.  2009. Poly-l-aspartic acid enhances and prolongs gentamicin-mediated suppression of the CFTR-G542X mutation in a cystic fibrosis mouse model. J. Biol. Chem. 284:6885–92 [Google Scholar]
  35. Du M, Keeling KM, Fan L, Liu X, Kovacs T. 35.  et al. 2006. Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model. J. Mol. Med. 84:573–82 [Google Scholar]
  36. Du M, Liu X, Welch EM, Hirawat S, Peltz SW, Bedwell DM. 36.  2008. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc. Natl. Acad. Sci. USA 105:2064–69 [Google Scholar]
  37. Durand S, Cougot N, Mahuteau-Betzer F, Nguyen CH, Grierson DS. 37.  et al. 2007. Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies. J. Cell Biol. 178:1145–60 [Google Scholar]
  38. Durand S, Lykke-Andersen J. 38.  2013. Nonsense-mediated mRNA decay occurs during eIF4F-dependent translation in human cells. Nat. Struct. Mol. Biol. 20:702–9 [Google Scholar]
  39. Eckford PD, Li C, Ramjeesingh M, Bear CE. 39.  2012. Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner. J. Biol. Chem. 287:36639–49 [Google Scholar]
  40. Fan-Minogue H, Du M, Pisarev AV, Kallmeyer AK, Salas-Marco J. 40.  et al. 2008. Distinct eRF3 requirements suggest alternate eRF1 conformations mediate peptide release during eukaryotic translation termination. Mol. Cell 30:599–609 [Google Scholar]
  41. Finkel RS. 41.  2010. Read-through strategies for suppression of nonsense mutations in Duchenne/Becker muscular dystrophy: aminoglycosides and ataluren (PTC124). J. Child Neurol. 25:1158–64 [Google Scholar]
  42. Floquet C, Rousset JP, Bidou L. 42.  2011. Readthrough of premature termination codons in the adenomatous polyposis coli gene restores its biological activity in human cancer cells. PLoS ONE 6:e24125 [Google Scholar]
  43. Frischmeyer-Guerrerio PA, Montgomery RA, Warren DS, Cooke SK, Lutz J. 43.  et al. 2011. Perturbation of thymocyte development in nonsense-mediated decay (NMD)-deficient mice. Proc. Natl. Acad. Sci. USA 108:10638–43 [Google Scholar]
  44. Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH. 44.  et al. 2005. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol. Cell 20:65–75 [Google Scholar]
  45. Giege R, Sissler M, Florentz C. 45.  1998. Universal rules and idiosyncratic features in tRNA identity. Nucleic Acids Res. 26:5017–35 [Google Scholar]
  46. Gilbert DN, Wood CA, Kohlhepp SJ, Kohnen PW, Houghton DC. 46.  et al. 1989. Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity. J. Infect. Dis. 159:945–53 [Google Scholar]
  47. Goldmann T, Overlack N, Möller F, Belakhov V, van Wyk M. 47.  et al. 2012. A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation. EMBO Mol. Med. 4:1186–99 [Google Scholar]
  48. Goldmann T, Overlack N, Wolfrum U, Nagel-Wolfrum K. 48.  2011. PTC124 mediated translational read-through of a nonsense mutation causing Usher type 1C. Hum. Gene Ther. 22:537–47 [Google Scholar]
  49. Goldmann T, Rebibo-Sabbah A, Overlack N, Nudelman I, Belakhov V. 49.  et al. 2010. Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina. Investig. Ophthalmol. Vis. Sci. 51:6671–80 [Google Scholar]
  50. Gong Q, Stump MR, Zhou Z. 50.  2011. Inhibition of nonsense-mediated mRNA decay by antisense morpholino oligonucleotides restores functional expression of hERG nonsense and frameshift mutations in long-QT syndrome. J. Mol. Cell. Cardiol. 50:223–29 [Google Scholar]
  51. Gonzalez S, Beghyn T, Jia J, Debreuck N, Berte G. 51.  et al. 2012. Rescue of nonsense mutations by amlexanox in human cells. Orphanet J. Rare Dis. 7:58 [Google Scholar]
  52. Guerin K, Gregory-Evans CY, Hodges MD, Moosajee M, Mackay DS. 52.  et al. 2008. Systemic aminoglycoside treatment in rodent models of retinitis pigmentosa. Exp. Eye Res. 87:197–207 [Google Scholar]
  53. Harmer SC, Mohal JS, Kemp D, Tinker A. 53.  2012. Readthrough of long-QT syndrome type 1 nonsense mutations rescues function but alters the biophysical properties of the channel. Biochem. J. 443:635–42 [Google Scholar]
  54. Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S. 54.  et al. 2007. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J. Clin. Pharmacol. 47:430–44 [Google Scholar]
  55. Hoshino S. 55.  2012. Mechanism of the initiation of mRNA decay: role of eRF3 family G proteins. Wiley Interdiscip. Rev. RNA 3:743–57 [Google Scholar]
  56. Howard M, Frizzell RA, Bedwell DM. 56.  1996. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat. Med. 2:467–69 [Google Scholar]
  57. Howard MT, Shirts BH, Petros LM, Flanigan KM, Gesteland RF, Atkins JF. 57.  2000. Sequence specificity of aminoglycoside-induced stop codon readthrough: potential implications for treatment of Duchenne muscular dystrophy. Ann. Neurol. 48:164–69 [Google Scholar]
  58. Huang C, Wu G, Yu YT. 58.  2012. Inducing nonsense suppression by targeted pseudouridylation. Nat. Protoc. 7:789–800 [Google Scholar]
  59. Hulka GF, Prazma J, Brownlee RE, Pulver S, Pillsbury HC. 59.  1993. Use of poly-l-aspartic acid to inhibit aminoglycoside cochlear ototoxicity. Am. J. Otol. 14:352–56 [Google Scholar]
  60. Huth ME, Ricci AJ, Cheng AG. 60.  2011. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Int. J. Otolaryngol. 2011:1–19 [Google Scholar]
  61. Ibba M, Hong KW, Sherman JM, Sever S, Soll D. 61.  1996. Interactions between tRNA identity nucleotides and their recognition sites in glutaminyl-tRNA synthetase determine the cognate amino acid affinity of the enzyme. Proc. Natl. Acad. Sci. USA 93:6953–58 [Google Scholar]
  62. Imataka H, Gradi A, Sonenberg N. 62.  1998. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. EMBO J. 17:7480–89 [Google Scholar]
  63. James PD, Raut S, Rivard GE, Poon MC, Warner M. 63.  et al. 2005. Aminoglycoside suppression of nonsense mutations in severe hemophilia. Blood 106:3043–48 [Google Scholar]
  64. Karijolich J, Yu YT. 64.  2011. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474:395–98 [Google Scholar]
  65. Keeling KM, Wang D, Dai Y, Murugesan S, Chenna B. 65.  et al. 2013. Attenuation of nonsense-mediated mRNA decay enhances in vivo nonsense suppression. PLoS ONE 8:e60478 [Google Scholar]
  66. Keiser NW, Engelhardt JF. 66.  2011. New animal models of cystic fibrosis: What are they teaching us?. Curr. Opin. Pulm. Med. 17:478–83 [Google Scholar]
  67. Kellermayer R, Szigeti R, Keeling KM, Bedekovics T, Bedwell DM. 67.  2006. Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey–Hailey disease. J. Investig. Dermatol. 126:229–31 [Google Scholar]
  68. Kerem E. 68.  2004. Pharmacologic therapy for stop mutations: How much CFTR activity is enough?. Curr. Opin. Pulm. Med. 10:547–52 [Google Scholar]
  69. Kerem E, Hirawat S, Armoni S, Yaakov Y, Shoseyov D. 69.  et al. 2008. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial. Lancet 372:719–27 [Google Scholar]
  70. Khajavi M, Inoue K, Lupski JR. 70.  2006. Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease. Eur. J. Hum. Genet. 14:1074–81 [Google Scholar]
  71. Kiselev AV, Ostapenko OV, Rogozhkina EV, Kholod NS, Seit Nebi AS. 71.  et al. 2002. Suppression of nonsense mutations in the dystrophin gene by a suppressor tRNA gene. Mol. Biol. 36:43–47 [Google Scholar]
  72. Konstan M, Accurso F, De Boeck K, Kerem E, Rowe S. 72.  et al. 2012. Targeting class 1 mutations: update on ataluren as a promising treatment for nonsense mutation cystic fibrosis. Pediatr. Pulmonol. 47:S35108–9 [Google Scholar]
  73. Kramer EB, Vallabhaneni H, Mayer LM, Farabaugh PJ. 73.  2010. A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae. RNA 16:1797–808 [Google Scholar]
  74. Laski FA, Ganguly S, Sharp PA, RajBhandary UL, Rubin GM. 74.  1989. Construction, stable transformation, and function of an amber suppressor tRNA gene in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 86:6696–98 [Google Scholar]
  75. Laurent G, Carlier MB, Rollman B, Van Hoof F, Tulkens P. 75.  1982. Mechanism of aminoglycoside-induced lysosomal phospholipidosis: in vitro and in vivo studies with gentamicin and amikacin. Biochem. Pharmacol. 31:3861–70 [Google Scholar]
  76. Lee HL, Dougherty JP. 76.  2012. Pharmaceutical therapies to recode nonsense mutations in inherited diseases. Pharmacol. Ther. 136:227–66 [Google Scholar]
  77. Linde L, Boelz S, Nissim-Rafinia M, Oren YS, Wilschanski M. 77.  et al. 2007. Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J. Clin. Investig. 117:683–92 [Google Scholar]
  78. Lynch SR, Puglisi JD. 78.  2001. Structural origins of aminoglycoside specificity for prokaryotic ribosomes. J. Mol. Biol. 306:1037–58 [Google Scholar]
  79. Lynch SR, Puglisi JD. 79.  2001. Structure of a eukaryotic decoding region A-site RNA. J. Mol. Biol. 306:1023–35 [Google Scholar]
  80. Makino H, Saijo T, Ashida Y, Kuriki H, Maki Y. 80.  1987. Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase. Int. Arch. Allergy Appl. Immunol. 82:66–71 [Google Scholar]
  81. Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W. 81.  et al. 2010. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann. Neurol. 67:771–80 [Google Scholar]
  82. Manuvakhova M, Keeling K, Bedwell DM. 82.  2000. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA 6:1044–55 [Google Scholar]
  83. Mattis VB, Ebert AD, Fosso MY, Chang CW, Lorson CL. 83.  2009. Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model. Hum. Mol. Genet. 18:3906–13 [Google Scholar]
  84. McCaughan KK, Brown CM, Dalphin ME, Berry MJ, Tate WP. 84.  1995. Translational termination efficiency in mammals is influenced by the base following the stop codon. Proc. Natl. Acad. Sci. USA 92:5431–35 [Google Scholar]
  85. McElroy SP, Nomura T, Torrie LS, Warbrick E, Gartner U. 85.  et al. 2013. A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. PLoS Biol. 11:e1001593 [Google Scholar]
  86. McIlwain DR, Pan Q, Reilly PT, Elia AJ, McCracken S. 86.  et al. 2010. Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay. Proc. Natl. Acad. Sci. USA 107:12186–91 [Google Scholar]
  87. Medghalchi SM, Frischmeyer PA, Mendell JT, Kelly AG, Lawler AM, Dietz HC. 87.  2001. Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability. Hum. Mol. Genet. 10:99–105 [Google Scholar]
  88. Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC. 88.  2004. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat. Genet. 36:1073–78 [Google Scholar]
  89. Metze S, Herzog VA, Ruepp MD, Muhlemann O. 89.  2013. Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways. RNA 19:1432–48 [Google Scholar]
  90. Mort M, Ivanov D, Cooper DN, Chuzhanova NA. 90.  2008. A meta-analysis of nonsense mutations causing human genetic disease. Hum. Mutat. 29:1037–47 [Google Scholar]
  91. Neri M, Torelli S, Brown S, Ugo I, Sabatelli P. 91.  et al. 2007. Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human. Neuromuscul. Disord. 17:913–18 [Google Scholar]
  92. Nguyen LS, Kim HG, Rosenfeld JA, Shen Y, Gusella JF. 92.  et al. 2013. Contribution of copy number variants involving nonsense-mediated mRNA decay pathway genes to neuro-developmental disorders. Hum. Mol. Genet. 22:1816–25 [Google Scholar]
  93. Nudelman I, Glikin D, Smolkin B, Hainrichson M, Belakhov V, Baasov T. 93.  2010. Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations. Bioorg. Med. Chem. 18:3735–46 [Google Scholar]
  94. Nudelman I, Rebibo-Sabbah A, Cherniavsky M, Belakhov V, Hainrichson M. 94.  et al. 2009. Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J. Med. Chem. 52:2836–45 [Google Scholar]
  95. Nudelman I, Rebibo-Sabbah A, Shallom-Shezifi D, Hainrichson M, Stahl I. 95.  et al. 2006. Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations. Bioorg. Med. Chem. Lett. 16:6310–15 [Google Scholar]
  96. Oussoren E, Keulemans J, van Diggelen OP, Oemardien LF, Timmermans RG. 96.  et al. 2013. Residual α-l-iduronidase activity in fibroblasts of mild to severe mucopolysaccharidosis type I patients. Mol. Genet. Metab. 109:377–81 [Google Scholar]
  97. Palmer E, Wilhelm JM. 97.  1978. Mistranslation in a eucaryotic organism. Cell 13:329–34 [Google Scholar]
  98. Palmer E, Wilhelm JM, Sherman F. 98.  1979. Phenotypic suppression of nonsense mutants in yeast by aminoglycoside antibiotics. Nature 277:148–50 [Google Scholar]
  99. Panchal RG, Wang S, McDermott J, Link CJ Jr. 99.  1999. Partial functional correction of xeroderma pigmentosum group A cells by suppressor tRNA. Hum. Gene Ther. 10:2209–19 [Google Scholar]
  100. Peltz SW, Morsy M, Welch EM, Jacobson A. 100.  2013. Ataluren as an agent for therapeutic nonsense suppression. Annu. Rev. Med. 64:407–25 [Google Scholar]
  101. Peltz SW, Welch EM, Jacobson A, Trotta CR, Naryshkin N. 101.  et al. 2009. Nonsense suppression activity of PTC124 (ataluren). Proc. Natl. Acad. Sci. USA 106:E64 [Google Scholar]
  102. Pichavant C, Aartsma-Rus A, Clemens PR, Davies KE, Dickson G. 102.  et al. 2011. Current status of pharmaceutical and genetic therapeutic approaches to treat DMD. Mol. Ther. 19:830–40 [Google Scholar]
  103. Piotrowska E, Jakobkiewicz-Banecka J, Baranska S, Tylki-Szymanska A, Czartoryska B. 103.  et al. 2006. Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur. J. Hum. Genet. 14:846–52 [Google Scholar]
  104. Politano L, Nigro G, Nigro V, Piluso G, Papparella S. 104.  et al. 2003. Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results. Acta Myol. 22:15–21 [Google Scholar]
  105. Qian Y, Guan MX. 105.  2009. Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness-associated mutation. Antimicrob. Agents Chemother. 53:4612–18 [Google Scholar]
  106. Ramsammy L, Josepovitz C, Lane B, Kaloyanides GJ. 106.  1990. Polyaspartic acid inhibits gentamicin-induced perturbations of phospholipid metabolism. Am. J. Physiol. 258:C1141–49 [Google Scholar]
  107. Rebibo-Sabbah A, Nudelman I, Ahmed ZM, Baasov T, Ben-Yosef T. 107.  2007. In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome. Hum. Genet. 122:373–81 [Google Scholar]
  108. Recht MI, Douthwaite S, Puglisi JD. 108.  1999. Basis for prokaryotic specificity of action of aminoglycoside antibiotics. EMBO J. 18:3133–38 [Google Scholar]
  109. Reilly SM, Chiang SH, Decker SJ, Chang L, Uhm M. 109.  et al. 2013. An inhibitor of the protein kinases TBK1 and IKK-varepsilon improves obesity-related metabolic dysfunctions in mice. Nat. Med. 19:313–21 [Google Scholar]
  110. Reiter RJ, Tan DX, Korkmaz A, Fuentes-Broto L. 110.  2011. Drug-mediated ototoxicity and tinnitus: alleviation with melatonin. J. Physiol. Pharmacol. 62:151–57 [Google Scholar]
  111. Rowe SM, Sloane P, Tang LP, Backer K, Mazur M. 111.  et al. 2011. Suppression of CFTR premature termination codons and rescue of CFTR protein and function by the synthetic aminoglycoside NB54. J. Mol. Med. 89:1149–61 [Google Scholar]
  112. Rowe SM, Verkman AS. 112.  2013. Cystic fibrosis transmembrane regulator correctors and potentiators. Cold Spring Harb. Perspect. Med. 3:a009761 [Google Scholar]
  113. Rufener SC, Muhlemann O. 113.  2013. eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells. Nat. Struct. Mol. Biol. 20:710–17 [Google Scholar]
  114. Salas-Marco J, Bedwell DM. 114.  2004. GTP hydrolysis by eRF3 facilitates stop codon decoding during eukaryotic translation termination. Mol. Cell. Biol. 24:7769–78 [Google Scholar]
  115. Salas-Marco J, Bedwell DM. 115.  2005. Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough. J. Mol. Biol. 348:801–15 [Google Scholar]
  116. Salas-Marco J, Fan-Minogue H, Kallmeyer AK, Klobutcher LA, Farabaugh PJ, Bedwell DM. 116.  2006. Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes. Mol. Cell. Biol. 26:438–47 [Google Scholar]
  117. Sanchez-Alcudia R, Perez B, Ugarte M, Desviat LR. 117.  2012. Feasibility of nonsense mutation readthrough as a novel therapeutical approach in propionic acidemia. Hum. Mutat. 33:973–80 [Google Scholar]
  118. Sangkuhl K, Schulz A, Rompler H, Yun J, Wess J, Schoneberg T. 118.  2004. Aminoglycoside-mediated rescue of a disease-causing nonsense mutation in the V2 vasopressin receptor gene in vitro and in vivo. Hum. Mol. Genet. 13:893–903 [Google Scholar]
  119. Sarkar C, Zhang Z, Mukherjee AB. 119.  2011. Stop codon read-through with PTC124 induces palmitoyl-protein thioesterase-1 activity, reduces thioester load and suppresses apoptosis in cultured cells from INCL patients. Mol. Genet. Metab. 104:338–45 [Google Scholar]
  120. Scheunemann AE, Graham WD, Vendeix FA, Agris PF. 120.  2010. Binding of aminoglycoside antibiotics to helix 69 of 23S rRNA. Nucleic Acids Res. 38:3094–105 [Google Scholar]
  121. Schiffelers R, Storm G, Bakker-Woudenberg I. 121.  2001. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies. J. Antimicrob. Chemother. 48:333–44 [Google Scholar]
  122. Schroers A, Kley RA, Stachon A, Horvath R, Lochmüller H. 122.  et al. 2006. Gentamicin treatment in McArdle disease: failure to correct myophosphorylase deficiency. Neurology 66:285–86 [Google Scholar]
  123. Schweingruber C, Rufener SC, Zund D, Yamashita A, Muhlemann O. 123.  2013. Nonsense-mediated mRNA decay: mechanisms of substrate mRNA recognition and degradation in mammalian cells. Biochim. Biophys. Acta 1829:612–23 [Google Scholar]
  124. Seoighe C, Gehring C. 124.  2010. Heritability in the efficiency of nonsense-mediated mRNA decay in humans. PLoS ONE 5:e11657 [Google Scholar]
  125. Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T. 125.  et al. 2010. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am. J. Respir. Crit. Care Med. 182:1262–72 [Google Scholar]
  126. Shalev M, Kandasamy J, Skalka N, Belakhov V, Rosin-Arbesfeld R, Baasov T. 126.  2013. Development of generic immunoassay for the detection of a series of aminoglycosides with 6′-OH group for the treatment of genetic diseases in biological samples. J. Pharm. Biomed. Anal. 75:33–40 [Google Scholar]
  127. Simon AJ, Lev A, Wolach B, Gavrieli R, Amariglio N. 127.  et al. 2010. The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients. PLoS ONE 5:e13659 [Google Scholar]
  128. Sutcliffe JA. 128.  2005. Improving on nature: antibiotics that target the ribosome. Curr. Opin. Microbiol. 8:534–42 [Google Scholar]
  129. Tan L, Narayan SB, Chen J, Meyers GD, Bennett MJ. 129.  2011. PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation. J. Inherit. Metab. Dis. 34:443–47 [Google Scholar]
  130. Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A. 130.  et al. 2007. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat. Genet. 39:1127–33 [Google Scholar]
  131. Tate WP, Poole ES, Horsfield JA, Mannering SA, Brown CM. 131.  et al. 1995. Translational termination efficiency in both bacteria and mammals is regulated by the base following the stop codon. Biochem. Cell Biol. 73:1095–103 [Google Scholar]
  132. Temple GF, Dozy AM, Roy KL, Kan YW. 132.  1982. Construction of a functional human suppressor tRNA gene: an approach to gene therapy for β-thalassaemia. Nature 296:537–40 [Google Scholar]
  133. Tomita K, Ueda T, Watanabe K. 133.  1999. The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria. Nucleic Acids Res. 27:1683–89 [Google Scholar]
  134. Usuki F, Yamashita A, Higuchi I, Ohnishi T, Shiraishi T. 134.  et al. 2004. Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease. Ann. Neurol. 55:740–44 [Google Scholar]
  135. Usuki F, Yamashita A, Kashima I, Higuchi I, Osame M, Ohno S. 135.  2006. Specific inhibition of nonsense-mediated mRNA decay components, SMG-1 or Upf1, rescues the phenotype of Ullrich disease fibroblasts. Mol. Ther. 14:351–60 [Google Scholar]
  136. Usuki F, Yamashita A, Shiraishi T, Shiga A, Onodera O. 136.  et al. 2013. Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity. Proc. Natl. Acad. Sci. USA 110:15037–42 [Google Scholar]
  137. Viegas MH, Gehring NH, Breit S, Hentze MW, Kulozik AE. 137.  2007. The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the nonsense mediated decay pathway. Nucleic Acids Res. 35:4542–51 [Google Scholar]
  138. Wang B, Yang Z, Brisson BK, Feng H, Zhang Z. 138.  et al. 2010. Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression. J. Appl. Physiol. 109:901–5 [Google Scholar]
  139. Wang D, Belakhov V, Kandasamy J, Baasov T, Li SC. 139.  et al. 2012. The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse. Mol. Genet. Metab. 105:116–25 [Google Scholar]
  140. Weischenfeldt J, Damgaard I, Bryder D, Theilgaard-Monch K, Thoren LA. 140.  et al. 2008. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. Genes Dev. 22:1381–96 [Google Scholar]
  141. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ. 141.  et al. 2007. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447:87–91 [Google Scholar]
  142. Wells SE, Hillner PE, Vale RD, Sachs AB. 142.  1998. Circularization of mRNA by eukaryotic translation initiation factors. Mol. Cell 2:135–40 [Google Scholar]
  143. Wilhelm JM, Jessop JJ, Pettitt SE. 143.  1978. Aminoglycoside antibiotics and eukaryotic protein synthesis: stimulation of errors in the translation of natural messengers in extracts of cultured human cells. Biochemistry 17:1149–53 [Google Scholar]
  144. Wilschanski M, Miller LL, Shoseyov D, Blau H, Rivlin J. 144.  et al. 2011. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. Eur. Respir. J. 38:59–69 [Google Scholar]
  145. Wilschanski M, Yahav Y, Yaacov Y, Blau H, Bentur L. 145.  et al. 2003. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N. Engl. J. Med. 349:1433–41 [Google Scholar]
  146. Wohlgemuth I, Pohl C, Mittelstaet J, Konevega AL, Rodnina MV. 146.  2011. Evolutionary optimization of speed and accuracy of decoding on the ribosome. Philos. Trans. R. Soc. Lond. B 366:2979–86 [Google Scholar]
  147. Yamashita A. 147.  2013. Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay. Genes Cells 18:161–75 [Google Scholar]
  148. Yang C, Feng J, Song W, Wang J, Tsai B. 148.  et al. 2007. A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin. Proc. Natl. Acad. Sci. USA 104:15394–99 [Google Scholar]
  149. Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R. 149.  2013. One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154:1370–79 [Google Scholar]
  150. Yukihara M, Ito K, Tanoue O, Goto K, Matsushita T. 150.  et al. 2011. Effective drug delivery system for Duchenne muscular dystrophy using hybrid liposomes including gentamicin along with reduced toxicity. Biol. Pharm. Bull. 34:712–16 [Google Scholar]
  151. Zhou Y, Jiang Q, Takahagi S, Shao C, Uitto J. 151.  2013. Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum. J. Investig. Dermatol. 133:2672–77 [Google Scholar]
  152. Zilberberg A, Lahav L, Rosin-Arbesfeld R. 152.  2010. Restoration of APC gene function in colorectal cancer cells by aminoglycoside- and macrolide-induced read-through of premature termination codons. Gut 59:496–507 [Google Scholar]
  153. Zund D, Gruber AR, Zavolan M, Muhlemann O. 153.  2013. Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3′ UTRs. Nat. Struct. Mol. Biol. 20:936–43 [Google Scholar]
/content/journals/10.1146/annurev-genom-091212-153527
Loading
Therapeutics Based on Stop Codon Readthrough
Annual Review of Genomics and Human Genetics 15, 371 (2014); https://doi.org/10.1146/annurev-genom-091212-153527
/content/journals/10.1146/annurev-genom-091212-153527
/content/journals/10.1146/annurev-genom-091212-153527
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error