Regulatable Gene Expression in Gene Therapy

Abstract

The regulation of exogenous gene expression may soon be a requirement for gene therapy approaches. Several systems promise to fulfill requirements for clinical applications.

Keywords: inducible gene expression; tetracycline; ecdyson; rapamycin/rapalogs; RU486; gene therapy; iathrogenic effects

References

Gossen M and Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline‐responsive promoters. Proceedings of the National Academy of Sciences of the United States of America 89(12): 5547–5551.

Gossen M, Freundlieb S, Bender G, et al. (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268: 1766–1769.

Liberles SD, Diver ST, Diver, Austin DJ, et al. (1997) Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three‐hybrid screen. Proceedings of the National Academy of Sciences of the United States of America 94(15): 7825–7830.

Magari SR, Rivera VM, Iuliucci JD, et al. (1997) Pharmacologic control of a humanized gene therapy system implanted into nude mice. Journal of Clinical Investigation 100: 2865–2872.

No D, Yao TP, Evans RM, et al. (1996) Ecdysone‐inducible gene expression in mammalian cells and transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 93(8): 3346–3351.

Pomerantz JL, Sharp PA, Pabo CO, et al. (1995) Structure‐based design of transcription factors. Science 267: 93–96.

Rivera VM, Clackson T, Natesan S, et al. (1996) A humanized system for pharmacologic control of gene expression. Nature Medicine 2(9): 1028–1032.

Rivera VM, Wang X, Wardwell S, et al. (2000) Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science 287: 826–830.

Rossi FM, Guicherit OM, Spicher A, et al. (1998) Tetracycline‐regulatable factors with distinct dimerization domains allow reversible growth inhibition by p16. Nature Genetics 20(4): 389–393.

Saez E, Nelson MC, Eshelman B, et al. (2000) Identification of ligands and coligands for the ecdysone‐regulated gene switch. Proceedings of the National Academy of Sciences of the United States of America 97(26): 14512–14517.

Vegeto E, Allan GF, Schrader WT et al. (1992) The mechanism of RU486 antagonism is dependent on the conformation of the carboxy‐terminal tail of the human progesterone receptor. Cell 69: 703–713.

Wang Y, Xu J, Pierson B, O'Malley BW and Tsai SY (1997) Positive and negative regulation of gene expression in eukaryotic cells with an inducible transcriptional regulator. Gene Therapy 4(5): 432–441.

Further Reading

Corbel SY and Rossi FM (2002) Latest developments and in vivo use of the Tet system: ex vivo and in vivo delivery of tetracycline‐regulated genes. Current Opinion in Biotechnology 13(5): 448–452.

Weber W, Fux C, Daoud‐el Baba M, et al. (2002) Macrolide‐based transgene control in mammalian cells and mice. Nature Biotechnology 20(9): 901–907.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Rossi, Fabio(Jan 2006) Regulatable Gene Expression in Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005748]