Versatile macrolide-responsive mammalian expression vectors for multiregulated multigene metabolic engineering.
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.
Weber
Wilfried
W
Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
Marty
René R
RR
Keller
Bettina
B
Rimann
Markus
M
Kramer
Beat P
BP
Fussenegger
Martin
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects* / Q000502:physiology*; D003001:Cloning, Molecular / Q000379:methods; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects*; D005818:Genetic Engineering / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D018942:Macrolides / Q000494:pharmacology; D005810:Multigene Family; D025361:Streptogramins / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods; D015533:Transcriptional Activation / Q000187:drug effects; D019076:Transgenes / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D018942:Macrolides; D025361:Streptogramins; D013752:Tetracycline