We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Gas-inducible transgene expression in mammalian cells and mice.
- Authors
Weber, Wilfried; Rimann, Markus; Spielmann, Manuela; Keller, Bettina; Daoud-El Baba, Marie; Aubel, Dominique; Weber, Cornelia C; Fussenegger, Martin
- 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.
- Publication
Nature biotechnology, 2004, Vol 22, Issue 11, p1440
- ISSN
1087-0156
- Publication type
Journal Article
- DOI
10.1038/nbt1021