title: Cosmetics-triggered percutaneous remote control of transgene expression in mice.
abstract: Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, 200241 Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Xie
authors.affiliation: Département Génie Biologique, Institut Universitaire de Technologie, F-69622 Villeurbanne Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Daoud El-Baba
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland Faculty of Science, University of Basel, CH-4058 Basel, Switzerland fussenegger@bsse.ethz.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003358:Cosmetics / Q000008:administration & dosage*; D006224:Cricetinae; D005786:Gene Expression Regulation; D051379:Mice; D009875:Operator Regions, Genetic; D010226:Parabens / Q000494:pharmacology*; D044224:Pseudomonas syringae / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D017592:Skin Care; D058615:Synthetic Biology / Q000379:methods; D014158:Transcription, Genetic; D019076:Transgenes
chemical_list: D003358:Cosmetics; D010226:Parabens; D012097:Repressor Proteins