title: The food additive vanillic acid controls transgene expression in mammalian cells and mice.
abstract: Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.
authors.affiliation: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Gitzinger
authors.forename: Christian
authors.initials: C
authors.lastname: Kemmer
authors.forename: David A
authors.initials: DA
authors.lastname: Fluri
authors.forename: Marie Daoud
authors.initials: MD
authors.lastname: El-Baba
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000818:Animals; D016466:CHO Cells; D016935:Caulobacter crescentus / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005503:Food Additives / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D006706:Homeostasis; D007700:Kinetics; D051379:Mice; D009875:Operator Regions, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D019076:Transgenes; D014641:Vanillic Acid / Q000494:pharmacology*
chemical_list: D005503:Food Additives; D014641:Vanillic Acid