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Targeted Genome Modification Via Triple Helix Formation

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Nucleic Acid Therapeutics in Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Over the last few decades, tremendous strides have been made in the identification of defective genes known to cause or contribute to the initiation or progression of different diseases. This research has led to new and innovative therapies in the treatment of disease. Traditionally, most active drugs are inhibitors of proteins. However, in recent years synthetic oligonucleotides have been developed as a means to rationally design therapeutic agents that selectively modulate gene expression. The ability to modulate a chosen gene’s function or expression for therapeutic use would be ideal to stimulate or restore the production of gene products whose absence leads to illness. For instance, the ability to correct or “repair” defective genes that are associated with inherited diseases would be of tremendous clinical value.

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References

  1. Vasquez KM, Wilson JH. Triplex-directed modification of genes and gene activity. Trends Biochem Sci 1998; 23:4–9.

    Article  PubMed  CAS  Google Scholar 

  2. Praseuth D, Guieysse AL, Helene C. Triple helix formation and the antigene strategy for sequence-specific control of gene expression. Biochim Biophys Acta 1999; 1489:181–206.

    Article  PubMed  CAS  Google Scholar 

  3. Chan PP, Glazer PM. Triplex DNA: fundamentals, advances, and potential applications for gene therapy. J Mol Med 1997; 75:267–82.

    Article  PubMed  CAS  Google Scholar 

  4. Curcio LD, Bouffard DY, Scanlon KJ. Oligonucleotides as modulators of cancer gene expression. Pharmacol Ther 1997; 74:317–32.

    Article  PubMed  CAS  Google Scholar 

  5. Letai AG, Palladino MA, Fromm E, Rizzo V, Fresco JR. Specificity in formation of triplestranded nucleic acid helical complexes: studies with agarose-linked polyribonucleotide affinity columns. Biochemistry 1988; 27:9108–12.

    Article  PubMed  CAS  Google Scholar 

  6. Francois JC, Saison-Behmoaras T, Helene C. Sequence-specific recognition of the major groove of DNA by oligodeoxynucleotides via triple helix formation. Footprinting studies. Nucleic Acids Res 1988; 16:11431–40.

    Article  PubMed  CAS  Google Scholar 

  7. Cooney M, Czernuszewicz G, Postel EH, Flint SJ, Hogan ME. Site-specific oligonucleotide binding represses transcription of the human c-myc gene in vitro. Science 1988; 241:456–9.

    Article  PubMed  CAS  Google Scholar 

  8. Le Doan T, Perrouault L, Praseuth D, et al. Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an <sub>oligo-[alpha]</sub>-t<sub>hymidylate</sub> covalently linked to an azidoproflavine derivative. Nucleic Acids Res 1987; 15:7749–60.

    Article  PubMed  Google Scholar 

  9. Moser HE, Dervan PB. Sequence-specific cleavage of double helical DNA by triple helix formation. Science 1987; 238:645–50.

    Article  PubMed  CAS  Google Scholar 

  10. Lee JS, Johnson DA, Morgan AR. Complexes formed by (pyrimidine)n . (purine)n DNAs on lowering the pH are three-stranded. Nucleic Acids Res 1979; 6:3073–91.

    Article  PubMed  CAS  Google Scholar 

  11. Povsic TJ, Dervan PB. Triple helix formation by oligonucleotides on DNA extended to the physiological range. J Am Chem Soc 1989; 111:3059–3061.

    Article  CAS  Google Scholar 

  12. Lacroix L, Lacoste J, Reddoch JF, et al. Triplex formation by oligonucleotides containing 5(1-propyny1)-2’-deoxyuridine: decreased magnesium dependence and improved intracellular gene targeting. Biochemistry 1999; 38:1893–901.

    Article  PubMed  CAS  Google Scholar 

  13. Beal PA, Dervan PB. Second structural motif for recognition of DNA by oligonucleotidedirected triple-helix formation. Science 1991; 251:1360–3.

    Article  PubMed  CAS  Google Scholar 

  14. Durland RH, Kessler DJ, Gunnell S, Duvic M, Pettitt BM, Hogan ME. Binding of triple helix forming oligonucleotides to sites in gene promoters. Biochemistry 1991; 30:9246–55.

    Article  PubMed  CAS  Google Scholar 

  15. Wang G, Levy DD, Seidman MM, Glazer PM. Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation. Mol Cell Biol 1995; 15:1759–68.

    PubMed  CAS  Google Scholar 

  16. Maher LJ, Wold B, Dervan PB. Inhibition of DNA binding proteins by oligonucleotidedirected triple helix formation. Science 1989; 245:725–30.

    Article  PubMed  CAS  Google Scholar 

  17. Maher LJ, Dervan PB, Wold BJ. Kinetic analysis of oligodeoxyribonucleotide-directed triplehelix formation on DNA. Biochemistry 1990; 29:8820–6.

    Article  PubMed  CAS  Google Scholar 

  18. Musso M, Wang JC, Van Dyke MW. In vivo persistence of DNA triple helices containing psoralen-conjugated oligodeoxyribonucleotides. Nucleic Acids Res 1996; 24:4924–32.

    Article  PubMed  CAS  Google Scholar 

  19. Svinarchuk F, Debin A, Bertrand JR, Malvy C. Investigation of the intracellular stability and formation of a triple helix formed with a short purine oligonucleotide targeted to the murine c-pim-1 proto-oncogene promotor. Nucleic Acids Res 1996; 24:295–302.

    Article  PubMed  CAS  Google Scholar 

  20. Rougee M, Faucon B, Mergny JL, et al. Kinetics and thermodynamics of triple-helix formation: effects of ionic strength and mismatches. Biochemistry 1992; 31:9269–78.

    Article  PubMed  CAS  Google Scholar 

  21. Hampel KJ, Crosson P, Lee JS. Polyamines favor DNA triplex formation at neutral pH. Biochemistry 1991; 30:4455–9.

    Article  PubMed  CAS  Google Scholar 

  22. Cheng AJ, Van Dyke MW. Monovalent cation effects on intermolecular purine-purine-pyrimidine triple-helix formation. Nucleic Acids Res 1993; 21:5630–5.

    Article  PubMed  CAS  Google Scholar 

  23. Olivas WM, Maher LJ. Overcoming potassium-mediated triplex inhibition. Nucleic Acids Res 1995; 23:1936–41.

    Article  PubMed  CAS  Google Scholar 

  24. Olivas WM, Maher L. Competitive triplex/quadruplex equilibria involving guanine-rich oligonucleotides. Biochemistry 1995; 34:278–84.

    Article  PubMed  CAS  Google Scholar 

  25. Sen D, Gilbert W. A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature 1990; 344:410–414.

    Article  PubMed  CAS  Google Scholar 

  26. Williamson JR, Raghuraman MK, Cech TR. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell 1989; 59:871–880.

    Article  PubMed  CAS  Google Scholar 

  27. Milligan JF, Krawczyk SH, Wadwani S, Matteucci MD. An anti-parallel triple helix motif with oligodeoxynucleotides containing 2’-deoxyguanosine and 7-deaza-2’-deoxyxanthosine. Nucleic Acids Res 1993; 21:327–33.

    Article  PubMed  CAS  Google Scholar 

  28. Faruqi AF, Krawczyk SH, Matteucci MD, Glazer PM. Potassium-resistant triple helix formation and improved intracellular gene targeting by oligodeoxyribonucleotides containing 7deazaxanthine. Nucleic Acids Res 1997; 25:633–40.

    Article  PubMed  CAS  Google Scholar 

  29. Havre PA, Gunther EJ, Gasparro FP, Glazer PM. Targeted mutagenesis of DNA using triple helix-forming oligonucleotides linked to psoralen. Proc Natl Acad Sci USA 1993; 90:7879–83.

    Article  PubMed  CAS  Google Scholar 

  30. Havre PA, Glazer PM. Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide. J Virol 1993; 67:7324–31.

    PubMed  CAS  Google Scholar 

  31. Sandor Z, Bredberg A. Repair of triple helix directed psoralen adducts in human cells. Nucleic Acids Res 1994; 22:2051–6.

    Article  PubMed  CAS  Google Scholar 

  32. Gasparro FP, Havre PA, Olack GA, Gunther EJ, Glazer PM. Site-specific targeting of psoralen photoadducts with a triple helix-forming oligonucleotide: characterization of psoralen monoadduct and crosslink formation. Nucleic Acids Res 1994; 22:2845–52.

    Article  PubMed  CAS  Google Scholar 

  33. Takasugi M, Guendouz A, Chassignol M, et al. Sequence-specific photo-induced cross-linking of the two strands of double-helical DNA by a psoralen covalently linked to a triple helixforming oligonucleotide. Proc Natl Acad Sci USA 1991; 88:5602–6.

    Article  PubMed  CAS  Google Scholar 

  34. Giovannangeli C, Thuong NT, Helene C. Oligodeoxynucleotide-directed photo-induced crosslinking of HIV proviral DNA via triple-helix formation. Nucleic Acids Res 1992; 20:4275–81.

    Article  PubMed  CAS  Google Scholar 

  35. Vasquez KM, Wang G, Havre PA, Glazer PM. Chromosomal mutations induced by triplexforming oligonucleotides in mammalian cells. Nucleic Acids Res 1999; 27:1176–81.

    Article  PubMed  CAS  Google Scholar 

  36. Glazer PM, Sarkar SN, Summers WC. Detection and analysis of UV-induced mutations in mammalian cell DNA using a lambda phage shuttle vector. Proc Natl Acad Sci USA 1986; 83:1041–4.

    Article  PubMed  CAS  Google Scholar 

  37. Gunther EJ, Murray NE, Glazer PM. High efficiency, restriction-deficient in vitro packaging extracts for bacteriophage lambda DNA using a new E.coli lysogen. Nucleic Acids Res 1993; 21:3903–4.

    Article  PubMed  CAS  Google Scholar 

  38. Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proc Natl Acad Sci USA 1997; 94:3122–7.

    Article  PubMed  CAS  Google Scholar 

  39. Majumdar A, Khorlin A, Dyatkina N, et al. Targeted gene knockout mediated by triple helix forming oligonucleotides. Nat Genet 1998; 20:212–4.

    Article  PubMed  CAS  Google Scholar 

  40. Wang G, Seidman MM, Glazer PM. Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair. Science 1996; 271:802–5.

    Article  PubMed  CAS  Google Scholar 

  41. Vasquez KM, Christensen J, Li L, Finch RA, Glazer PM. Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions. Proc Natl Acad Sci USA 2002; 99:5848–53.

    Article  PubMed  CAS  Google Scholar 

  42. Vasquez KM, Narayanan L, Glazer PM. Specific mutations induced by triplex-forming oligonucleotides in mice. Science 2000; 290:530–3.

    Article  PubMed  CAS  Google Scholar 

  43. Zendegui JG, Vasquez KM, Tinsley JH, Kessler DJ, Hogan ME. In vivo stability and kinetics of absorption and disposition of 3’ phosphopropyl amine oligonucleotides. Nucleic Acids Res 1992; 20:307–14.

    Article  PubMed  CAS  Google Scholar 

  44. Vasquez KM, Marburger K, Intody Z, Wilson JH. Manipulating the mammalian genome by homologous recombination. Proc Natl Acad Sci USA 2001; 98:8403–10.

    Article  PubMed  CAS  Google Scholar 

  45. Rouet P, Smih F, Jasin M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol 1994; 14:8096–106.

    PubMed  CAS  Google Scholar 

  46. Saffran WA, Cantor CR, Smith ED, Magdi M. Psoralen damage-induced plasmid recombination in Saccharomyces cerevisiae: dependence on RAD1 and RAD52. Mutat Res 1992; 274:1–9.

    Article  PubMed  CAS  Google Scholar 

  47. Wang YY, Maher VM, Liskay RM, McCormick JJ. Carcinogens can induce homologous recombination between duplicated chromosomal sequences in mouse L cells. Mol Cell Biol 1988; 8:196–202.

    PubMed  CAS  Google Scholar 

  48. Tsujimura T, Maher VM, Godwin AR, Liskay RM, McCormick JJ. Frequency of intra-chro-mosomal homologous recombination induced by UV radiation in normally repairing and excision repair-deficient human cells. Proc Natl Acad Sci USA 1990; 87:1566–70.

    Article  PubMed  CAS  Google Scholar 

  49. Faruqi AF, Seidman MM, Segal DJ, Carroll D, Glazer PM. Recombination induced by triplehelix-targeted DNA damage in mammalian cells. Mol Cell Biol 1996; 16:6820–8.

    PubMed  CAS  Google Scholar 

  50. Faruqi AF, Datta HJ, Carroll D, Seidman MM, Glazer PM. Triple-helix formation induces recombination in mammalian cells via a nucleotide excision repair-dependent pathway. Mol Cell Biol 2000; 20:990–1000.

    Article  PubMed  CAS  Google Scholar 

  51. Luo Z, Macris MA, Faruqi AF, Glazer PM. High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells. Proc Natl Acad Sci USA 2000; 97:9003–8.

    Article  PubMed  CAS  Google Scholar 

  52. Chan PP, Lin M, Faruqi AF, Powell J, Seidman MM, Glazer PM. Targeted correction of an episomal gene in mammalian cells by a short DNA fragment tethered to a triplex-forming oligonucleotide. J Biol Chem 1999; 274:11541–8.

    Article  PubMed  CAS  Google Scholar 

  53. Datta HJ, Chan PP, Vasquez KM, Gupta RC, Glazer PM. Triplex-induced recombination in human cell-free extracts. Dependence on XPA and HsRad51. J Biol Chem 2001; 276:18018–23.

    Article  PubMed  CAS  Google Scholar 

  54. Egholm M, Buchardt 0, Christensen L, et al. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 1993; 365:566–8.

    Article  PubMed  CAS  Google Scholar 

  55. Peffer NJ, Hanvey JC, Bisi JE, et al. Strand-invasion of duplex DNA by peptide nucleic acid oligomers. Proc Natl Acad Sci USA 1993; 90:10648–52.

    Article  PubMed  CAS  Google Scholar 

  56. Egholm M, Christensen L, Dueholm KL, Buchardt 0, Coull J, Nielsen PE. Efficient pHindependent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Nucleic Acids Res 1995; 23:217–22.

    Article  PubMed  CAS  Google Scholar 

  57. Larsen HJ, Nielsen PE. Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: sequence-specific suicide transcription. Nucleic Acids Res 1996; 24:458–63.

    Article  PubMed  CAS  Google Scholar 

  58. Bentin T, Nielsen PE. Enhanced peptide nucleic acid binding to supercoiled DNA: possible implications for DNA “breathing” dynamics. Biochemistry 1996; 35:8863–9.

    Article  PubMed  CAS  Google Scholar 

  59. Praseuth D, Grigoriev M, Guieysse AL, et al. Peptide nucleic acids directed to the promoter of the alpha-chain of the interleukin-2 receptor. Biochim Biophys Acta 1996; 1309:226–38.

    Article  PubMed  CAS  Google Scholar 

  60. Nielsen PE, Egholm M, Berg RH, Buchardt 0. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA. Nucleic Acids Res 1993; 21:197–200.

    Article  PubMed  CAS  Google Scholar 

  61. Faruqi AF, Egholm M, Glazer PM. Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells. Proc Natl Acad Sci USA 1998; 95:1398–403.

    Article  PubMed  CAS  Google Scholar 

  62. Hobbs CA, Yoon K. Differential regulation of gene expression in vivo by triple helix-forming oligonucleotides as detected by a reporter enzyme. Antisense Res Dev 1994; 4:1–8.

    PubMed  CAS  Google Scholar 

  63. Porumb H, Gousset H, Letellier R, et al. Temporary ex vivo inhibition of the expression of the human oncogene HER2 (NEU) by a triple helix-forming oligonucleotide. Cancer Res 1996; 56:515–22.

    PubMed  CAS  Google Scholar 

  64. Macaulay VM, Bates PJ, McLean MJ, et al. Inhibition of aromatase expression by a psoralenlinked triplex-forming oligonucleotide targeted to a coding sequence. FEBS Lett 1995; 372:222–8.

    Article  PubMed  CAS  Google Scholar 

  65. Kochetkova M, Shannon ME DNA triplex formation selectively inhibits granulocyte-mac-rophage colony-stimulating factor gene expression in human T cells. J Biol Chem 1996; 271:14438–44.

    Article  PubMed  CAS  Google Scholar 

  66. Liu Y, Began R. Improved Intracellular Delivery of Oligonucleotides by Square Wave Electroporation. Antisense & Nucleic Acid Drug Development 2001; 11:7–14.

    Article  CAS  Google Scholar 

  67. Pooga M, Hallbrink M, Zorko M, Langel U. Cell penetration by transportan. Faseb J 1998; 12:67–77.

    PubMed  CAS  Google Scholar 

  68. Derossi D, Joliot AH, Chassaing G, Prochiantz A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 1994; 269:10444–50.

    PubMed  CAS  Google Scholar 

  69. Tung CH, Wang J, Leibowitz MJ, Stein S. Dual-specificity interaction of HIV-1 TAR RNA with tat peptide-oligonucleotide conjugates. Bioconjug Chem 1995; 6:292–5.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Faye A. Rogers PhD
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  2. Peter M. Glazer MD, PhD
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Editors and Affiliations

  1. Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Alan M. Gewirtz MD

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Rogers, F.A., Glazer, P.M. (2004). Targeted Genome Modification Via Triple Helix Formation. In: Gewirtz, A.M. (eds) Nucleic Acid Therapeutics in Cancer. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-777-2_3

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  • DOI: https://doi.org/10.1007/978-1-59259-777-2_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9858-5

  • Online ISBN: 978-1-59259-777-2

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