Skip to main content

Genome Modification by Triplex-Forming Oligonucleotides

  • Chapter
Triple Helix Forming Oligonucleotides

Part of the book series: Perspectives in Antisense Science ((DARE,volume 2))

Abstract

Gene expression is a process that is first regulated at the level of DNA. By introducing modifications in specific DNA sequences of living cells, it is possible to permanently alter the expression of genes relevant to disease. Triplex technology offers an approach to site-specific genome modification in mammalian cells such that it is possible to direct damage to specific sites in the DNA via triplex-forming oligonucleotides (TFOs) and thereby induce mutations or sensitize a site for gene replacement via homologous recombination [also reviewed in (1, 2)]. The work reported in this chapter describes the initial steps toward the development of a triplex-based strategy for site-specific genome modification via targeted mutagenesis and recombination.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chan, P. P. and Glazer, P. M. (1997). Triplex DNA: fundamentals, advances, and potential applications for gene therapy. J. Mol. Med. 75, 267–282.

    Article  PubMed  CAS  Google Scholar 

  2. Vasquez, K. M. and Wilson, J. H. (1998). Triplex-directed modification of genes and gene activity. Trends Biochem. Sci. 23, 4–9.

    Article  PubMed  CAS  Google Scholar 

  3. Frank-Kamenetskii, M. D. and Mirkin, S. M. (1995). Triplex DNA structures. Ann. Rev. Biochem. 64, 65–95.

    Article  PubMed  CAS  Google Scholar 

  4. Postel, E. H., Flint, S. J., Kessler, D. J. and Hogan, M. E. (1991). Evidence that a triplex-forming oligodeoxyribonucleotide binds to the c-myc promoter in HeLa cells, thereby reducing c-myc mRNA levels. Proc. Natl. Acad. Sci. USA 88, 8227–8231.

    Article  PubMed  CAS  Google Scholar 

  5. Beal, P. A. and Dervan, P. B. (1991). Second structural motif for recognition of DNA by oligonucleotide-directed triple-helix formation. Science 251, 1360–1363.

    Article  PubMed  CAS  Google Scholar 

  6. Havre, P. A. and Glazer, P. M. (1993). Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide. J Virol 67, 7324–7331.

    PubMed  CAS  Google Scholar 

  7. Havre, P. A., Gunther, E. J., Gasparro, F. P. and Glazer, P. M. (1993). Targeted mutagenesis of DNA using triple helix-forming oligonucleotides linked to psoralen. Proc. Natl. Acad. Sci. USA 90, 7879–7883.

    Article  PubMed  CAS  Google Scholar 

  8. Wang, G., Levy, D. D., Seidman, M. M. and Glazer, P. M. (1995). Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation. Mol. Cell. Biol. 15, 1759–1768.

    PubMed  CAS  Google Scholar 

  9. Thaler, D. S. and Stahl, F. W. (1988). DNA double-chain breaks in recombination of phage lambda and of yeast. Ann. Rev. Genet. 22, 169–197.

    Article  PubMed  CAS  Google Scholar 

  10. Capecchi, M. R. (1989). Altering the genome by homologous recombination. Science 244, 1288–1292.

    Article  PubMed  CAS  Google Scholar 

  11. Bollag, R. J., Waldman, A. S. and Liskay, R. M. (1989). Homologous recombination in mammalian cells. Ann. Rev. Genet. 23, 199–225.

    Article  PubMed  CAS  Google Scholar 

  12. Roth, D. B. and Wilson J. H. (1986). Non-homologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol. Cell Biol. 6, 4295–4304.

    PubMed  CAS  Google Scholar 

  13. Averbeck, D. (1985). Relationship between lesions photoinduced by mono-and bi-functional furocoumarins in DNA and genotoxic effects in diploid yeast. Mutat. Res. 151, 217–233.

    Article  PubMed  CAS  Google Scholar 

  14. Kucherlapati, R. S., Eves, E. M., Song, K. Y., Morse, B. S. and Smithies, O. (1984). Homologous recombination between plasmids in mammalian cells can be enhanced by treatment of input DNA. Proc. Natl. Acad. Sci. USA 81, 3153–3157.

    Article  PubMed  CAS  Google Scholar 

  15. Brenner, D. A., Smigocki, A. C. and Camerini-Otero, R. D. (1985). Effect of insertions, deletions and double-strand breaks on homologous recombination in mouse L cells. Mol. Cell Biol. 5, 684–691.

    PubMed  CAS  Google Scholar 

  16. Wake, C. T., Vernaleone, F. and Wilson, J. H. (1985). Topological requirements for homologous recombination among DNA molecules transfected into mammalian cells. Mol. Cell Biol. 5, 2080–2089.

    PubMed  CAS  Google Scholar 

  17. Sargent, R. G., Brenneman, M. A. and Wilson, J. H. (1997). Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination. Mol. Cell Biol. 17, 267–277.

    PubMed  CAS  Google Scholar 

  18. Friedberg, E. C., Walker, G. C. and Siede, W. (1995). DNA repair and mutagenesis. American Society for Microbiology, Washington, DC.

    Google Scholar 

  19. Bramson, J. and Panasci, L. C. (1993). Effect of ERCC-1 overexpression on sensitivity of Chinese hamster ovary cells to DNA damaging agents. Cancer Res. 53, 3237–3240.

    PubMed  CAS  Google Scholar 

  20. Narayanan, L., Fritzell, J. A., Baker, S. M., Liskay, R. M. and Glazer, P. M. (1997). Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene, Pms2. Proc. Natl. Acad. Sci. USA 94, 3122–3127.

    Article  PubMed  CAS  Google Scholar 

  21. Glazer, P. M., Sarkar, S. N. and Summers, W. C. (1986). Detection and analysis of UV-induced mutations in mammalian cell DNA using a lambda phage shuttle vector. Proc. Natl. Acad. Sci. USA 83, 1041–1044.

    Article  PubMed  CAS  Google Scholar 

  22. Gunther, E. J., Murray, N. E. and Glazer, P. M. (1993). High efficiency, restriction-deficient in vitro packaging extracts for bacteriophage lambda DNA using a new E. coli lysogen. Nucleic Acids Res. 21, 3903–3904.

    Article  PubMed  CAS  Google Scholar 

  23. Faruqi, A. F., Seidman, M. M., Segal, D. J., Carroll, D. and Glazer, P. M. (1996). Recombination induced by triple helix-targeted DNA damage in mammalian cells. Mol. Cell. Biol. 16, 6820–6828.

    PubMed  CAS  Google Scholar 

  24. Adair, G. M., Nairn, R. S., Wilson, J. H., Seidman, M. M., Brotherman, K. A., MacKinnon, C. and Scheerer J. B. (1989). Targeted homologous recombination at the endogenous adenine phosphoribosyltransferase locus in Chinese hamster cells. Proc. Natl. Acad. Sci. USA 86, 4574–4578.

    Article  PubMed  CAS  Google Scholar 

  25. Pennington, S. L. and Wilson, J. H. (1991). Gene targeting in Chinese hamster ovary cells is conservative. Proc. Natl. Acad. Sci. USA 88, 9498–9502.

    Article  PubMed  CAS  Google Scholar 

  26. Sargent, R. G., Merrihew, R. V., Nairn, R., Adair, G., Meuth, M. and Wilson, J. H. (1996). The influence of a (GT)29 microsatellite sequence on homologous recombination in the hamster adenine phosphoribosyltransferase gene. Nucleic Acids Res. 24, 746–753.

    Article  PubMed  CAS  Google Scholar 

  27. Merrihew, R. V., Sargent, R. G. and Wilson, J. H. (1995). Efficient modification of the APRT gene by FLP/FRT site-specific targeting. Somat. Cell Mol. Genet. 21, 299–307.

    Article  PubMed  CAS  Google Scholar 

  28. Wang, G., Seidman, M. M. and Glazer P. M. (1996). Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair. Science 271, 802–805.

    Article  PubMed  CAS  Google Scholar 

  29. Hanawalt, P. C. (1994). Transcription-coupled repair and human disease. Science 266, 1957–1958.

    Article  PubMed  CAS  Google Scholar 

  30. Vasquez, K. M., Wang, G., Havre, P. A. and Glazer P. M. (1998). Chromosomal mutations induced by triplex-forming oligonucleotides in mammalian cells. Submitted.

    Google Scholar 

  31. Sancar, A. (1994). Mechanisms of DNA excision repair. Science 266, 1954–1956.

    Article  PubMed  CAS  Google Scholar 

  32. Sancar, A. and Tang, M. S. (1993). Nucleotide excision repair. Photochem.. Photobiol. 57, 905–921.

    Google Scholar 

  33. Sladek, F. M., Munn, M. M., Rupp, W. D. and Howard-Flanders, P. (1989). In vitro repair of psoralen-DNA cross-links by RecA, UvrABC, and the 5′-exonuclease of DNA polymerase I. J. Biol. Chem. 264, 6755–6765.

    PubMed  CAS  Google Scholar 

  34. Sandor, Z. and Bredberg, A.. (1994). Repair of triple helix directed psoralen adducts in human cells. Nucleic Acids Res. 22, 2051–2056.

    Article  PubMed  CAS  Google Scholar 

  35. Sandor, Z. and Bredberg, A. (1995). Deficient DNA repair of triple helix-directed double psoralen damage in human cells. FEBS Lett. 374, 287–291.

    Article  PubMed  CAS  Google Scholar 

  36. Degols, G., Clarenc, J. P., Lebleu, B. and Leonetti, J. P. (1994). Reversible inhibition of gene expression by a psoralen functionalized triple helix forming oligonucleotide in intact cells. J. Biol. Chem. 269, 16933–16937.

    PubMed  CAS  Google Scholar 

  37. Wang, G. and Glazer, P. M. (1995). Altered repair of targeted psoralen photoadducts in the context of an oligonucleotide-mediated triple helix. J. Biol. Chem. 270, 22595–22601.

    Article  PubMed  CAS  Google Scholar 

  38. Hacia, J. G., Dervan, P. B. and Wold, B. J. (1994). Inhibition of Klenow fragment DNA polymerase on double-helical templates by oligonucleotide-directed triple-helix formation. Biochemistry 33, 6192–6200.

    Article  PubMed  CAS  Google Scholar 

  39. Sandor, Z. and Bredberg, A. (1995). Triple helix directed psoralen adducts induce a low frequency of recombination in an SV-40 shuttle vector. Biochim. Biophys. Acta 1263, 235–240.

    Article  PubMed  Google Scholar 

  40. Vasquez, K. M., Wensel, T. G., Hogan, M. E. and Wilson, J. H. (1995). High-affinity triple helix formation by synthetic oligonucleotides at a site within a selectible mammalian gene. Biochemistry 34, 7243–7251.

    Article  PubMed  CAS  Google Scholar 

  41. Vasquez, K. M., Wensel, T. G., Hogan, M. E. and Wilson, J. H. (1996). High-efficiency triple-helix-mediated photo-cross-linking at a targeted site within a selectable mammalian gene. Biochemistry 35, 10712–10719.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Vasquez, K.M., Glazer, P.M. (1999). Genome Modification by Triplex-Forming Oligonucleotides. In: Malvy, C., Harel-Bellan, A., Pritchard, L.L. (eds) Triple Helix Forming Oligonucleotides. Perspectives in Antisense Science, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5177-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5177-5_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7358-2

  • Online ISBN: 978-1-4615-5177-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics