ArticleProceedings of the National Academy of Sciences of the United States of America2009
Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 109 citations in OpenAlex.
- A synthetic angiotensin II/ACE2-based hormone shunt controlling experimental hypertension.Nature communications · 2026Article
- A Natural Sweetener-inducible Genetic Switch Controls Therapeutic Protein Expression in Mammals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Designing modular genetic sensors with TtgR/AcrR family transcriptional regulators by using a statistical and data-driven approach.Nucleic acids research · 2025Article
- Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins.Nature biomedical engineering · 2025Article
- Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Engineering natural molecule-triggered genetic control systems for tunable gene- and cell-based therapies.Synthetic and systems biotechnology · 2023Article
- Controlling therapeutic protein expression via inhalation of a butter flavor molecule.Nucleic acids research · 2023Article
- Technological advances in mosquito olfaction neurogenetics.Trends in genetics : TIG · 2023Review
- Review
- RuX: A Novel, Flexible, and Sensitive Mifepristone-Induced Transcriptional Regulation System.International journal of cell biology · 2023Article
- Regulation of Transgene Expression by the Natural Sweetener Xylose.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.International journal of molecular sciences · 2022Article
- Autonomous push button-controlled rapid insulin release from a piezoelectrically activated subcutaneous cell implant.Science advances · 2022Article
- Spatial control of gene expression in flies using bacterially derived binary transactivation systems.Insect molecular biology · 2021Article
- Phloretin, an Apple Phytoalexin, Affects the Virulence and Fitness ofFrontiers in plant science · 2021Article
- Construction of Caffeine-Inducible Gene Switches in Mammalian Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Review
- Small-molecule inducible transcriptional control in mammalian cells.Critical reviews in biotechnology · 2020Review
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate.Science advances · 2020Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adjustable control of therapeutic transgenes in engineered cell implants after transdermal and topical delivery of nontoxic trigger molecules would increase convenience, patient compliance, and elimination of hepatic first-pass effect in future therapies. Pseudomonas putida DOT-T1E has evolved the flavonoid-triggered TtgR operon, which controls expression of a multisubstrate-specific efflux pump (TtgABC) to resist plant-derived defense metabolites in its rhizosphere habitat. Taking advantage of the TtgR operon, we have engineered a hybrid P. putida-mammalian genetic unit responsive to phloretin. This flavonoid is contained in apples, and, as such, or as dietary supplement, regularly consumed by humans. The engineered mammalian phloretin-adjustable control element (PEACE) enabled adjustable and reversible transgene expression in different mammalian cell lines and primary cells. Due to the short half-life of phloretin in culture, PEACE could also be used to program expression of difficult-to-produce protein therapeutics during standard bioreactor operation. When formulated in skin lotions and applied to the skin of mice harboring transgenic cell implants, phloretin was able to fine-tune target genes and adjust heterologous protein levels in the bloodstream of treated mice. PEACE-controlled target gene expression could foster advances in biopharmaceutical manufacturing as well as gene- and cell-based therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.