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Control of transgene expression in mammalian cells

Part 1. Genetics

1.7. Gene Therapy

Basic Techniques and Approaches

  1. Beat P. Kramer,
  2. Martin Fussenegger

Published Online: 15 JAN 2005

DOI: 10.1002/047001153X.g107402

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Kramer, B. P. and Fussenegger, M. 2005. Control of transgene expression in mammalian cells. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 1:1.7:104.

Author Information

  1. Institute of Chemical and Bio-Engineering, Zurich, Switzerland

Publication History

  1. Published Online: 15 JAN 2005

Abstract

Spacio-temporal adjustment of therapeutic transgene expression represents a fundamental technology for modern gene therapy since it enables precise in vivo dosing of protein therapeutics to manage an optimal therapeutic range, adaptation to specific disease dynamics, or resetting of molecular interventions as appropriate. Heterologous transcription control systems capitalizing on (1) prokaryotic antibiotic response regulons evolved to manage bacterial adaptation to macrolide, streptogramin, and tetracycline antibiotics, (2) (modified) hormone receptors specific for estradiol, progesterone, or ecdysone derivatives, or (3) chemically induced dimerization of protein domains prevailed in animal studies, and are currently considered for clinical trials. Since sustained administration of clinically licensed, small-molecule drugs for transgene expression fine-tuning may result in side effects, systems responsive to nucleic acids or physical parameters including light, temperature, and electromagnetic fields are in preclinical development.

Keywords:

  • heterologous gene regulation;
  • inducible/repressible promoter;
  • tetracycline;
  • erythromycin;
  • pristinamycin;
  • rapamycin;
  • ecdysone;
  • RU486;
  • estrogen