Tobacco smoke as inducer for gas phase-controlled transgene expression in mammalian cells and mice.
Capitalizing on components evolved to metabolize ethanol in Aspergillus nidulans, we previously designed the first molecular gas-gene expression interface using gaseous acetaldehyde as the major inducer. This fungus-derived acetaldehyde-inducible gene regulation (AIR) system operated perfectly and enabled precise and reversible transgene expression dosing in a variety of mammalian cells. We now validate the use of mainstream cigarette smoke typically containing acetaldehyde at regulation-effective nontoxic concentrations as a noninvasive modality to adjust transgene transcription in mammalian cells and mice. Indeed, tobacco smoke-induced expression fine-tuning of AIR-driven transgenes was successful in mammalian cells. Even mice implanted with cells transgenic for AIR-controlled SEAP (human secreted alkaline phosphatase) production showed serum SEAP levels correlating with inhaled tobacco smoke doses. Tobacco smoke-controlled gene expression may foster clinical opportunities as well as advances in understanding smoke-related pathologies.
Weber
Wilfried
W
Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
Spielmann
Manuela
M
Daoud El-Baba
Marie
M
Keller
Bettina
B
Aubel
Dominique
D
Fussenegger
Martin
M
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005740:Gases / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018014:Gene Transfer Techniques; D051379:Mice; D044367:Phase Transition; D011994:Recombinant Proteins / Q000096:biosynthesis*; D012906:Smoke; D014162:Transfection / Q000379:methods*; D019076:Transgenes / Q000187:drug effects*
D005740:Gases; D011994:Recombinant Proteins; D012906:Smoke; D000079:Acetaldehyde