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Nat Biotechnol. 2004 Nov;22(11):1440-4. Epub 2004 Oct 17.

Gas-inducible transgene expression in mammalian cells and mice.

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  • 1Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg HCI F115, CH-8093 Zurich, Switzerland.

Abstract

We describe the design and detailed characterization of a gas-inducible transgene control system functional in different mammalian cells, mice and prototype biopharmaceutical manufacturing. The acetaldehyde-inducible AlcR-P(alcA) transactivator-promoter interaction of the Aspergillus nidulans ethanol-catabolizing regulon was engineered for gas-adjustable transgene expression in mammalian cells. Fungal AlcR retained its transactivation characteristics in a variety of mammalian cell lines and reversibly adjusted transgene transcription from chimeric mammalian promoters (P(AIR)) containing P(alcA)-derived operators in a gaseous acetaldehyde-dependent manner. Mice implanted with microencapsulated cells engineered for acetaldehyde-inducible regulation (AIR) of the human glycoprotein secreted placental alkaline phosphatase showed adjustable serum phosphatase levels after exposure to different gaseous acetaldehyde concentrations. AIR-controlled interferon-beta production in transgenic CHO-K1-derived serum-free suspension cultures could be modulated by fine-tuning inflow and outflow of acetaldehyde-containing gas during standard bioreactor operation. AIR technology could serve as a tool for therapeutic transgene dosing as well as biopharmaceutical manufacturing.

PMID:
15502819
[PubMed - indexed for MEDLINE]
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