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In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence

Nature volume 372, pages 642–645 (1994)Cite this article

Abstract

A DNA-binding peptide comprising three zinc-fingers has been engineered to bind specifically to a unique nine-base-pair region of a BCR–ABL fusion oncogene in preference to the parent genomic sequences. Binding to the target oncogene in chromosomal DNA is possible in transformed cells in culture, and results in blockage of transcription. Consequently, murine cells rendered independent of growth factors by the action of the oncogene revert to factor dependence upon transient transfection with a vector expressing the peptide.

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References

  1. Choo, Y. & Klug, A. Proc. natn. Acad. Sci. U.S.A. 91, 11163–11167 (1994).

    Article  ADS  CAS  Google Scholar 

  2. Choo, Y. & Klug, A. Proc. natn. Acad. Sci. U.S.A. 91, 11168–11172 (1994).

    Article  ADS  CAS  Google Scholar 

  3. Nowell, P. C. & Hungerford, D. A. Science 132, 1197–1200 (1960).

    Google Scholar 

  4. Bartram, C. R. et al. Nature 306, 277–280 (1983).

    Article  ADS  CAS  Google Scholar 

  5. Groffen, J. et al. Cell 36, 93–99 (1984).

    Article  CAS  Google Scholar 

  6. Shtivelman, E., Lifshitz, B., Gale, R. P. & Canaani, E. Nature 315, 550–554 (1985).

    Article  ADS  CAS  Google Scholar 

  7. Konopka, J. B., Watanabe, S. M. & Witte, O. N. Cell 37, 1035–1042 (1984).

    Article  CAS  Google Scholar 

  8. Hermans, A. et al. Cell 51, 33–40 (1987).

    Article  CAS  Google Scholar 

  9. Kurzrock, R. et al. Nature 325, 631–635 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Daley, G. Q. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 85, 9312–9316 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Heisterkamp, N. et al. Nature 344, 251–253 (1990).

    Article  ADS  CAS  Google Scholar 

  12. Miller, J., McLachlan, A. D. & Klug, A. EMBO J. 4, 1609–1614 (1985).

    Article  CAS  Google Scholar 

  13. Berg, J. M. Proc. natn. Acad. Sci. U.S.A. 85, 99–102 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Lee, M. S., Gippert, G. P., Soman, K. V., Case, D. A. & Wright, P. E. Science 245, 635–637 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Pavletich, N. P. & Pabo, C. O. 252, 809–817 (1991).

  16. Choo, Y. & Klug, A. Nucleic Acids Res. 21, 3341–3346 (1993).

    Article  CAS  Google Scholar 

  17. Rebar, E. J. & Pabo, C. O. Science 263, 671–673 (1994).

    Article  ADS  CAS  Google Scholar 

  18. Jamieson, A. C., Kim, S.-H. & Wells, J. A. Biochemistry 33, 5689–5695 (1994).

    Article  CAS  Google Scholar 

  19. Desjarlais, J. R. & Berg, J. M. Proc. natn. Acad. Sci. U.S.A. 89, 7345–7349 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Kadonaga, J. T., Carner, K. R., Masiarz, F. R. & Tjian, R. Cell 51, 1079–1090 (1987).

    Article  CAS  Google Scholar 

  21. Christy, B. A., Lau, L. F. & Nathans, D. Proc. natn. Acad. Sci. U.S.A. 85, 7857–7861 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Fairall, L., Harrison, S. D., Travers, A. A. & Rhodes, D. J. molec. Biol. 226, 349–366 (1992).

    Article  CAS  Google Scholar 

  23. Hawkins, R. E., Russell, S. J. & Winter, G. J. molec. Biol. 226, 889–896 (1992).

    Article  CAS  Google Scholar 

  24. Fields, S. Methods 5, 116–124 (1993).

    Article  CAS  Google Scholar 

  25. Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).

    Article  CAS  Google Scholar 

  26. Kalderon, D., Roberts, B. L., Richardson, W. D. & Smith, A. E. Cell 499–509 (1984).

    Article  CAS  Google Scholar 

  27. Evan, G. I., Lewis, G. K., Ramsay, G. & Bishop, J. M. Molec. cell. Biol. 5, 3610–3616 (1985).

    Article  CAS  Google Scholar 

  28. Palacios, R. & Steinmetz, M. Cell 41, 727–734 (1985).

    Article  CAS  Google Scholar 

  29. Stein, C. A. & Cheng, Y. Science 261, 1004–1012 (1993).

    Article  ADS  CAS  Google Scholar 

  30. Cooney, M., Czernuszewicz, G., Postel, E. H., Flint, S. J. & Hogan, M. E. Science 245, 725–730 (1988).

    Google Scholar 

  31. Seipel, K., Georgiev, O. & Shaffner, W. EMBO J. 11, 4961–4968 (1992).

    Article  CAS  Google Scholar 

  32. Herschbach, B. M., Arnaud, M. B. & Johnson, A. D. Nature 370, 309–311 (1994).

    Article  ADS  CAS  Google Scholar 

  33. Luscher, B., Mitchell, P. J., Williams, T. & Tjian, R. Genes Dev. 3, 1507–1517 (1989).

    Article  CAS  Google Scholar 

  34. Mizushima, S. & Shigezaku, N. Nucleic Acids Res. 18, 5322 (1990).

    Article  CAS  Google Scholar 

  35. de Wet, J. R., Wood, K. V., de Luca, M., Helinski, D. R. & Subramani, S. Molec. cell. Biol. 7, 725–737 (1987).

    Article  CAS  Google Scholar 

  36. Sanchez-Garcia, I., Osada, H., Forster, A. & Rabbitts, T. H. EMBO J. 12, 4243–4250 (1993).

    Article  CAS  Google Scholar 

  37. Sadowski, I., Brendan, B., Broad, P. & Hollis, M. Gene 118, 137–141 (1992).

    Article  CAS  Google Scholar 

  38. Sanchez-Garcia, I. & Rabbitts, T. H. Proc. natn. Acad. Sci. U.S.A. 91, 7869–7873 (1994).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Yen Choo, Isidro Sánchez-García & Aaron Klug

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  1. Yen Choo
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  2. Isidro Sánchez-García
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  3. Aaron Klug
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Choo, Y., Sánchez-García, I. & Klug, A. In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. Nature 372, 642–645 (1994). https://doi.org/10.1038/372642a0

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