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Versatile macrolide-responsive mammalian expression vectors for multiregulated multigene metabolic engineering
Authors:Weber Wilfried  Marty René R  Keller Bettina  Rimann Markus  Kramer Beat P  Fussenegger Martin
Affiliation:Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
Abstract:
The novel macrolide-inducible and -repressible mammalian gene regulation systems (E.REX) have been cloned into a variety of sophisticated expression configurations including (1) multi-purpose expression vectors, (2) pTRIDENT-based artificial operons, (3) dual-regulated expression strategies for independent control of two different transgenes, (4) autoregulated vectors for one-step installation of adjustable multigene expression, and (5) oncoretroviral and lentiviral plasmids for transduction of macrolide-, streptogramin- and tetracycline-dependent transactivators and production of cell lines supporting independent control of three different transgenes. This vector portfolio represents a construction kit-like toolbox for efficient installation of adjustable gene expression responsive to clinically licensed antibiotics and enables the design of multiregulated multigene metabolic engineering strategies required for biopharmaceutical manufacturing, gene therapy, and tissue engineering.
Keywords:gene regulation system  macrolide antibiotics  erythromycin  streptogramin antibiotics  tetracycline antibiotics  E.REX  PIP system  TET system  dual‐regulated expression  triple‐regulated expression  pTRIDENT  pDuoRex  pTriRex  pTwin  pRetroTriRex  gene therapy  tissue engineering
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