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Gas-inducible transgene expression in mammalian cells and mice.
Journal article

Gas-inducible transgene expression in mammalian cells and mice.

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  • 2004-10-27
Published in:
  • Nature biotechnology. - 2004
Acetaldehyde
Alkaline Phosphatase
Animals
Cell Line
Cricetinae
Dose-Response Relationship, Drug
Female
GPI-Linked Proteins
Gases
Gene Expression Regulation
Genetic Enhancement
Humans
Isoenzymes
Mice
Protein Engineering
Recombinant Proteins
Transgenes
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/67111
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