Gas-inducible transgene expression in mammalian cells and mice

被引：0
|
作者：
Wilfried Weber
Markus Rimann
Manuela Spielmann
Bettina Keller
Marie Daoud-El Baba
Dominique Aubel
Cornelia C Weber
Martin Fussenegger
机构：
[1] Institute for Chemical and Bio-Engineering,Département Génie Biologique
[2] Swiss Federal Institute of Technology,undefined
[3] ETH Hoenggerberg HCI F115,undefined
[4] Institut Universitaire de Technologie,undefined
[5] IUTA,undefined
[6] 43 Boulevard du 11 Novembre 1918,undefined
[7] Institute for Biomedical Engineering,undefined
[8] Swiss Federal Institute of Technology,undefined
[9] ETH Zentrum,undefined
来源：
Nature Biotechnology | 2004年 / 22卷
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摘要：
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-PalcA transactivator-promoter interaction of the Aspergillus nidulans ethanol-catabolizing regulon1 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 (PAIR) containing PalcA-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-β 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.
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页码：1440 / 1444
页数：4
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