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Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells

Abstract

Patients with certain genetic disorders can be cured by bone marrow transplantation1,2. However, as prospective donors do not exist for most patients with potentially curable genetic abnormalities, an alternative treatment for such patients involves the transfer of cloned genes into the patient's haematopoietic stem cells followed by re-infusion of the treated cells3. Retroviral vectors provide an efficient means for transferring genes into mammalian cells and have been used to transfer genes into mouse haematopoietic cells4–8. We have now produced amphotropic retroviral vectors containing either the bacterial gene for neomycin resistance or a mutant dihydrofolate reductase gene that confers resistance to methotrexate and have used these vectors to infect and confer drug resistance to human haematopoietic progenitor cells in vitro. Transfer could be demonstrated in the absence of helper virus by using an amphotropic retrovirus packaging cell line, PA12 (ref. 9). These studies are an important step towards the eventual application of retrovirus-mediated gene transfer to human gene therapy and for molecular approaches to the study of human haematopoiesis.

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References

  1. Bortin, M. M. & Rim, A. A. J. Am. med. Ass. 238, 591–600 (1977).

    Article  CAS  Google Scholar 

  2. Thomas, E. D. et al. Lancet ii, 227–229 (1982).

    Article  Google Scholar 

  3. Anderson, W. F. Science 226, 401–409 (1984).

    Article  CAS  ADS  Google Scholar 

  4. Joyner, A. Keller, R. A., Phillips, A. & Bernstein, A. Nature 305, 556–558 (1983).

    Article  CAS  ADS  Google Scholar 

  5. Miller, A. D., Eckner, R. J., Jolly, D. J., Friedmann, T. & Verma, I. Science 225, 630–632 (1984).

    Article  CAS  ADS  Google Scholar 

  6. Williams, D. A., Lemischka, I. R., Nathan, D. G. & Mulligan, R. C. Nature 310, 476–480 (1984).

    Article  CAS  ADS  Google Scholar 

  7. Dick, J. E., Magli, R. C., Huszar, D., Phillips, R. A. & Bernstein, A. Cell 42, 1–79 (1985).

    Article  Google Scholar 

  8. Keller, G., Paige, C., Gilboa, E. & Wagner, E. F. Nature 318, 149–154 (1985).

    Article  CAS  ADS  Google Scholar 

  9. Miller, A. D., Law, M. F. & Verma, I. M. Molec. cell. Biol 5, 431–437 (1985).

    Article  CAS  Google Scholar 

  10. Levitt, P. & Quesenberry, L. New Engl. J. Med. 301, 755–760, 819–823, 868–872 (1979).

    Article  Google Scholar 

  11. Pike, B. L. & Robinson, W. A. J. cell. Physiol. 76, 77–84 (1970).

    Article  CAS  Google Scholar 

  12. Stephenson, J. R., Axelrad, A. A., McLeod, D. L. & Shreeve, M. M. Proc. natn. Acad. Sci. U.S.A. 68, 1542–1546 (1971).

    Article  CAS  ADS  Google Scholar 

  13. Fauser, A. A. & Messner, H. A. Blood 52, 1243–1248 (1978).

    CAS  PubMed  Google Scholar 

  14. Colbère-Garapin, F., Horodniceanu, F., Kourilsky, P. & Garapin, A. C. J. molec. Biol. 150, 1–14 (1981).

    Article  Google Scholar 

  15. Simonsen, C. C. & Levinson, A. D. Proc. natn. Acad. Sci. U.S.A. 80, 2495–2499 (1983).

    Article  CAS  ADS  Google Scholar 

  16. Miller, A. D., Trauber, D. R. & Buttimore, C. Somatic Cell molec. Genet. 12, 175–183 (1986).

    Article  CAS  Google Scholar 

  17. Koizumi, S. et al. Expl Hemat. 8, 635–640 (1980).

    CAS  Google Scholar 

  18. Chabner, B. & Young, R. C. J. clin. Invest. 52, 1804–1811 (1973).

    Article  CAS  Google Scholar 

  19. Kwok, W. W., Schuening, F., Stead, R.B. & Miller, A. D. Proc. natn. Acad. Sci. U.S.A. (in the press).

  20. Rothstein, L., Pierce, J. H., Klassen. V. & Greenberger, J. Blood 65, 744–752 (1985).

    CAS  PubMed  Google Scholar 

  21. Gruber, H. E. et al. Science 230, 1057–1061 (1985).

    Article  CAS  ADS  Google Scholar 

  22. Mann, R., Mulligan, R. C. & Baltimore, D. Cell 33, 153–159 (1983).

    Article  CAS  Google Scholar 

  23. Andrews, R. G., Torok-Storb, B. & Bernstein, I. D. Blood 62, 124–132 (1983).

    CAS  PubMed  Google Scholar 

  24. Schlunk, T. & Schleyer, M. Expl Hemat. 8, 179–184 (1980).

    CAS  Google Scholar 

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Hock, R., Miller, A. Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells. Nature 320, 275–277 (1986). https://doi.org/10.1038/320275a0

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