Application of Tetracycline Regulatable Systems for Gene Therapy

  • Delphine Bohl
  • Jean-Michel Heard
Conference paper
Part of the NATO ASI Series book series (volume 105)

Abstract

Many diseases candidates for gene therapy require that the therapeutic gene expression level is controlled in order to ensure biological efficacy and to prevent toxic effects. Various systems have been described which allow transcriptional regulation by artificial chimeric transactivators in mammalian cells. This paper describes the tetracycline regulatable systems and discuss their potential application for gene therapy.

Keywords

Zinc Toxicity Estrogen Leukemia Cadmium 

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References

  1. Ackland-Berglund, C. E., and Leib, D. A. (1995). Efficacy of Tetracycline-Controlled Gene Expression is Influenced by Cell Type. BioTechniques 18, 196–200.PubMedGoogle Scholar
  2. Agarwal, M. L., Agarwal, A., Taylor, W. R., and Stark, G. R. (1995). p53 controls both the G2/M and the G1 cell cycle checkpoint and mediates reversible growth arrest in human fibroblasts. Proc. Natl. Acad. Sci. USA 92, 8493–8497.PubMedCrossRefGoogle Scholar
  3. Blanchard, K. L., Acquaviva, A. M., Galson, D. L., and Bunn, H. F. (1992). Hypoxic induction of the human erythropoietin gene: cooperation between the promoter and enhancer, each of which contains steroid receptor response elements. Mol. Cell. Biol. 12, 5373–5385.PubMedGoogle Scholar
  4. Blau, C. A., Peterson, K. R., Drachman, J. G., and Spencer, D. M. (1997). A proliferation switch for genetically modified cells. Proc. Natl. Acad. Sci. 94, 3076–3081.PubMedCrossRefGoogle Scholar
  5. Bohl, D., and Heard, J. (1997). Modulation of erythropoietin delivery from engineered muscles in mice. Human Gene Ther. 8, 195–204.CrossRefGoogle Scholar
  6. Bohl, D., Naffakh, N., and Heard, J. M. (1997). Long term control of erythropoietin secretion levels by tetracycline in mice transplanted with engineered primary myoblasts. Nature Med. 3, 299–312.PubMedCrossRefGoogle Scholar
  7. Cao, J., Park, I., Cooper, A., and Sodroski, J. (1996). Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1. J. Virol. 70, 1340–1354.PubMedGoogle Scholar
  8. Cayrot, C., and Flemington, E. K. (1995). Identification of cellular target genes of the Epstein-Barr virus transactivator Zta activation of transforming growth factor beta igh3 (TGF-beta igh3) and TGF-betal. J. Virol. 69, 206–212.Google Scholar
  9. Cox, L. A., and Adrian, G. S. (1993). Posttranscriptional regulation of chimeric human transferrin genes by iron. Biochemistry 32, 4738–4745.PubMedCrossRefGoogle Scholar
  10. Davis, J. L., Gross, P. R., and Danos, O. (1997). Development and characterization of a translationally regulated retroviral vector. Abstract, Keystone Meeting, April 13–19, 21.Google Scholar
  11. Degenkolb, J., Takahashi, M., Ellestad, G. A., and Hillen, W. (1991). Structural requirements of tetracycline-tet repressor interaction: determination of equilibrim binding constants for tetracycline analogs with the tet repressor. Antimicrob. Agents Chemother. 35, 1591–1595.PubMedGoogle Scholar
  12. Delort, J. P., and Capecchi, M, R. (1996). TAXI/UAS: a molecular switch to control expression of gens m vivo. Hum. Gene Ther. 7, 809–820.PubMedCrossRefGoogle Scholar
  13. Deuschle, U., Meyer, W. K.-H., and Thiesen, H.-J. (1995). Tetracycline-Reversible Silencing of Eukaryotic Promoters. Mol. Cell. Biol. 15, 1907–1914.PubMedGoogle Scholar
  14. Dingermann, T., Frank-Stoll, U., Werner, H., Wissman, A., Hillen, W., Jacquet, M., and Marschalek, R. (1992). RNA polymerase III catalysed transcription can be regulated in Saccharomyces cerevisiae by the bacterial tetracycline repressor-operator system. EMBO J. 11, 1487–1492.PubMedGoogle Scholar
  15. Dingermann, T., Werner, H., Schütz, A., Zündorf, I., Nerke, K., Knecht, D., and Marschalek, R. (1992). Establishment of a system for conditional gene expression using an inducible tRNA suppressor gene. Mol. Cell. Biol. 12, 4038–4045.PubMedGoogle Scholar
  16. Efrat, S., Fusco-DeMane, D., Lemberg, H., Al Emran, O., and Wang, X. (1995). Conditional transformation of a pancreatic b-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Proc. Natl. Acad. Sci. USA 92, 3576–3580.PubMedCrossRefGoogle Scholar
  17. Emerman, M., and Temin, H. M. (1984). Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell 39, 459–467.CrossRefGoogle Scholar
  18. Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D., and Chambon, P. (1996). Ligand-activated site-specific recombinasion in mice. Proc. Natl. Acad. Sci. 93, 10887–10890.PubMedCrossRefGoogle Scholar
  19. Fishman, G. I., Kaplan, M. L., and Buttrick, P. M. (1994). Tetracycline-regulated cardiac gene expression in vivo. J. Clin. Invest. 93, 1864–1868.PubMedCrossRefGoogle Scholar
  20. Freiberg, R. A., Ho, S. N., and Khavari, P. A. (1997). Transcriptional control in keratinocytes and fibroblasts using synthetic ligands. J. Clin. Invest. 99, 2610–2615.PubMedCrossRefGoogle Scholar
  21. Freiberg, R. A., Spencer, D. M., Choate, K. A., Peng, P. D., Schreiber, S. L., Crabtree, G. R., and Khavari, P. A. (1996). Specific triggering of the fas signal transduction pathway in normal human keratinocytes. J. Biol. Chem. 271, 31666–31669.PubMedCrossRefGoogle Scholar
  22. Furth, P. A., St. Onge, L., Böger, H., Grass, P., Gossens, M., Kistner, A., Bujard, H., and Hennighausen, L. (1994). Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc. Natl. Acad. Sci. USA 91, 9302–9306.PubMedCrossRefGoogle Scholar
  23. Gatz, C., Kaiser, A., and Wendenburg, R. (1991). Regulation of a modified CaMV 35S promoter by the Tn10- encoded Tet repressor in transgenic tobacco. Mol. Gen. Genet. 227, 229–237.PubMedCrossRefGoogle Scholar
  24. Goossen, B., Wright Caughman, S., Harford, J. B., Klausner, R. D., and Hentze, M. W. (1990). Translational repression by a complex between the iron-responsive element of ferritin mRNA and its specific cytoplasmic binding protein is position dependent in vivo. EMBO J. 9, 4127–4133.PubMedGoogle Scholar
  25. Gossen, M., and Bujard, H. (1993). Anhydrotetracyclin, a novel effector for tetracycline controlled gene expression in eukaryotic cells. Nucl. Acid Res. 21, 4411–4412.CrossRefGoogle Scholar
  26. Gossen, M., and Bujard, H. (1992). Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA 89, 5547–5551.PubMedCrossRefGoogle Scholar
  27. Gossen, M., Freundlieb, S., Bender, G., Müller, G., Hillen, W., and Bujard, H. (1995). Transcriptional activation by tetracyclines in mammalian cells. Science 268, 1766–1769.PubMedCrossRefGoogle Scholar
  28. Ho, D. Y., McLaughlin, J. R., and Sapolsky, R. M. (1996). Inducible gene expression from defective herpes simplex virus vectors using tetracycline-responsive promoter system. Mol. Brain Res. 41, 200–209.PubMedCrossRefGoogle Scholar
  29. Hoffman, A., Nolan, G., and Blau, H. B. (1996). Rapid retroviral delivery of tetracycline-inducible genes in a single autoregulatory cassette. Proc. Natl. Acad. Sci. USA 93, 5185–5190.CrossRefGoogle Scholar
  30. Hoshimaru, M., Ray, J., Sah, D. W. Y., and Gage, F. H. (1996). Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene. Proc. Natl. Acad. Sci. USA 93, 1518–1523.PubMedCrossRefGoogle Scholar
  31. Howe, J. R., Skryabin, B. V., Belcher, S. M., Zerillo, C. A., and Sclimauss, C. (1995). The responsiveness of a tetracycline-sensitive expression system differs in different cell lines. J. Biol. Chem. 270, 14168–14178.PubMedCrossRefGoogle Scholar
  32. Hu, M. C. T., and Davidson, N. (1990). A combination of derepression of the lac operator-repressor system with positive induction by glucocorticoid and metal ions provides a high-level-inducible gene expression system based on the human metallothionein-IIA promoter. Mol. Cell. Biol. 10, 6141–6451.PubMedGoogle Scholar
  33. Hwang, J. J., Scuric, Z., and Anderson, W. F. (1996). Novel retroviral vector transferring a suicide gene and a selectable marker gene with enhanced gene expression by using a tetracyclineresponsive expression system. J. Virol. 70, 8138–8141.PubMedGoogle Scholar
  34. Iida, A., Chen, S. T., Friedmann, T., and Yee, J. K. (1996). Inducible gene expression by retrovirus-mediated transfer of a modified tetracycline-regulated system. J. Virol. 70, 6054–6059.PubMedGoogle Scholar
  35. Ingles, C. J., Shales, M., Cress, W. D., Triezenberg, S. J., and Greenblatt, J. (1991). Reduced Binding of TFID to Transcriptionally compromised Mutants of VP16. Nature 351, 588–590.PubMedCrossRefGoogle Scholar
  36. Israel, D., and Kaufman, R. J. (1989). Highly Inducible Expression From Vectors Containing Multiple GRE’s in CHO Cells Overexpressing the Glucocorticoid Receptor. Nucleic. Acids. Res. 17, 4589–4604.PubMedCrossRefGoogle Scholar
  37. Jiang, B., Rue, E., Wang, G. L., Roe, R., and Semenza, G. L. (1996). Dimerization, DNA binding and transactivation properties of hypoxia-inducible factor 1. J. Bio. Chem. 271, 17771–17778.CrossRefGoogle Scholar
  38. Kenan, D. J., Tasi, D. E., and Keene, J. D. (1994). Exploring molecular diversity with combinatorial shape libraries. TIBS 19, 57–64.PubMedGoogle Scholar
  39. Kim, H. J., Gatz, C., Hillen, W., and Jones, T. R. (1995). Tetracycline repressor-regulated gene repression in recombinant human cytomegalovirus. J. Virol. 69, 2565–2573.PubMedGoogle Scholar
  40. Lin, Y.-S., Ha, I., Maldonado, E., Reinberg, D., and Green, M. R. (1991). Binding of General Transcription Factors TFIIB to an Acidic Activating Region. Nature 353, 569–571.PubMedCrossRefGoogle Scholar
  41. Madan, A., and Curtin, P. T. (1993). A 24-base-pair sequence 3′ to the human erythropoietin gene contains a hypoxia-responsive transcriptional enhancer. Proc. Natl. Acad. Sci. USA 90, 3928–3932.PubMedCrossRefGoogle Scholar
  42. Mader, S., and White, J. S. (1993). A Steroid-Inducible Promoter for the Controlled Overexpression of Cloned Genes in Eukaryotic Cells. Proc. Natl. Acad. Sci. USA 90, 5603–5607.PubMedCrossRefGoogle Scholar
  43. Mahfoudi, A., Roulet, E., Dauvois, S., Parker, M. G., and Whali, W. (1995). Specific mutations in the estrogen receptor change the properties of antiestrogens to full agonists. Proc. Natl. Acad. Sci. 92, 4206–4210.PubMedCrossRefGoogle Scholar
  44. Mayo, K. E., Warren, R., and Palmiter, R. D. (1982). The Mouse Metallothionein-I Gene Is Transcriptionally Regulated by Cadmium Following Transfaction into Human or Mouse Cells. Cell 29, 99–108.PubMedCrossRefGoogle Scholar
  45. No, D., Yao, T., and Evans, R. M. (1996). Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. 93, 3346–3351.PubMedCrossRefGoogle Scholar
  46. Passman, R. S., and Fishman, G. I. (1994). Regulated expression of foreign genes in vivo after germline transfer. J. Clin. Invest. 94, 2421–2425.PubMedCrossRefGoogle Scholar
  47. Paulus, W., Baur, I., Boyce, F. M., Breakefield, X. O., and Reeves, S. A. (1996). Self-contained, tetracyclineregulated retroviral system for gene delivery to mammalian cells. J. Virol. 70, 62–67.PubMedGoogle Scholar
  48. Resnitzky, D., Hengst, L., and Reed. S. I. (1995). Cyclin A-associated kinase activity is rate limiting for entrance into S phase and is negatively regulated in G1 by p27Kipl. Mol. Cell. Biol. 15, 4347–4352.PubMedGoogle Scholar
  49. Rivera, V. M., Clackson, T., Natesan, S., Pollock, R., Amara, J. F., Keenan, T., Magari, S. R., Phillips, T., Courage, N. L., Cerasoli, F., Dennis, A. H., and Gilman, M. (1996). A humanized system for pharmacologic control of gene expression. Nat. Med. 2, 1028–1032.PubMedCrossRefGoogle Scholar
  50. Rizzino, A., and Miller, K. (1995). The function of inducible promoter systems in F9 embryonal carcinoma cells. Exp. Cell Res. 218, 144–150.PubMedCrossRefGoogle Scholar
  51. Röder, F. T., Schmülling, T., and Gatz, C. (1994). Efficiency of the tetracycline-dependent gene expression system: complete suppression and efficient induction of the rolB phenotype in transgenic plants. Mol. Gen. Genet. 243, 32–38.PubMedCrossRefGoogle Scholar
  52. Schaack, J., Guo, X., Ho, Y., Karlok, M., Chen, C., and Oemelles, D. (1995). Adenovirus type 5 precursor terminal protein-expressing 293 and HeLa cell lines. J. Virol. 69, 4079–4085.PubMedGoogle Scholar
  53. Schultze, N., Burki, Y., Lang, Y., Certa, U., and Bluethmann, H. (1996). Efficient control of gene expression by single step integration of the tetracycline system in transgenic mice. Nature Biotech. 14, 499–505.CrossRefGoogle Scholar
  54. Schweinfest, C. W., Jorcyk, C. L., Fujiwara, S., and Papas, T. S. (1988). A heat-shock inductible eukaryotic expression vector. Gene 71, 207–210.PubMedCrossRefGoogle Scholar
  55. Searl, P. F., Stuart, G. W., and Palmiter, R. D. (1985). Building a Metal-Responsive Promoter With Synthetic Regulatory Elements. Mol. Cell. Biol. 5, 1480–1489.Google Scholar
  56. Shan, B., and Lee, W. (1994). Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol. Cell Biol. 14, 8166–8173.PubMedGoogle Scholar
  57. Shockett, P., Difilippantonio, M., Heilman, N., and Schatz, D. (1995). A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice. Proc. Natl. Acad. Sci. USA 92, 6522–6526.PubMedCrossRefGoogle Scholar
  58. Spencer, D. M., Beishaw, P. J., Chen, L., Ho, S. N., Randazzo, F., Crabtree, G. R., and Schreiber, S. L. (1996). Functional analysis of fas signaling in vivo using synthetic inducers of dimerization. Current Biol. 6, 839–847.CrossRefGoogle Scholar
  59. Staeheli, P., Danielson, P., Haller, O., and Sutcliffe, J. G. (1986). Transcriptional activation of the mouse Mx gene by type 1 interferon. Mol. Cel. Biol. 6, 4770–4774.Google Scholar
  60. Totzke, F., Marmé, D., and Hug, R. (1992). Inducible expression of human phospholipase C-g2 and its activation by platelet-derived growth factor B-chain homodimer and platelet-derived growth factor A-chain homodimer in transfected NIH 3T3. Eur. J. Biochem. 203, 633–639.PubMedCrossRefGoogle Scholar
  61. Triezenberg, S. J., Kingsbury, R. C., and McKnight, S. L. (1988). Functional Dissection of VP16, the Trans- Activator of Herpes Simplex Virus Immediate Early Gene Expression. Genes and development 2, 718–729.PubMedCrossRefGoogle Scholar
  62. Wang, G. L., and Semenza, G. L. (1993). General involvment of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc. Natl. Acad. Sci. USA 90, 4304–4308.PubMedCrossRefGoogle Scholar
  63. Wang, Y., O’Malley Jr., B. W., Tasai, S. Y., and O’Malley, B. W. (1994). A regulatory system for use in gene transfer. Proc Natl. Acad. Sci. USA 91, 8180–8184.PubMedCrossRefGoogle Scholar
  64. Watsuji, T., Okamoto, Y., Emi, N., Katsuoka, Y., and Hagiwara, M. (1997). Controlled gene expression with a reverse tetracycline-regulated retroviral vector system. Bioche. Biophys. Res. Comm. 234, 769–773.CrossRefGoogle Scholar
  65. Wimmel, A., Lucibello, F. C., Sewing, A., Adolph, S., and Muller, R. (1994). Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E. Oncogene 9, 995–997.PubMedGoogle Scholar
  66. Wirtz, E., and Clayton, C. (1995). Inducible gene expression in trypanosomes mediated by a prokaryotic repressor. Science 268, 1179–1183.PubMedCrossRefGoogle Scholar
  67. Wurm, F. M., Gwinn, K. A., and Kingston, R. E. (1986). Inducible overexpression of a mouse c-myc protein in mammalian cells. Proc. Natl. Sci. 83, 5414–5418.CrossRefGoogle Scholar
  68. Xu, L., Yee, J. K., Wolff, J. A., and Friedmann, T. (1989). Factors influencing long-term stability of Moloney leukemia virus-based vectors. Virology 171, 331–341.PubMedCrossRefGoogle Scholar
  69. Yarranton, G. T. (1992). Inducible vectors for expression in mammalian cells. Cur. Op. in Biotech. 3, 506–511.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Delphine Bohl
    • 1
  • Jean-Michel Heard
    • 1
  1. 1.Laboratoire Rétrovirus et Transfert GénétiqueInstitut PasteurParis cedex 15France

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