Caffeine-inducible gene switches controlling experimental diabetes
Bojar D, Scheller L, Hamri GC, Xie M, Fussenegger M
Nature communications · 74 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- European Research Council
- Grants
- European Research Council (ProNet, 321381)
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-06-07 · Nat Commun · vol. 9 · issue 1 · p. 2318
- Publisher
- Nature Portfolio
- Cited
- 86 citations · more than 98% of similar papers · 7.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 59 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Pancreatic function and diabetes · Coffee research and impacts · CRISPR and Genetic Engineering
- Keywords
- Caffeine, Diabetes mellitus, Computational biology, Chemistry, Biology, Medicine, Endocrinology
- MeSH
- cell line, animals, mice, inbred c57bl, mice, transgenic, humans, mice, diabetes mellitus, experimental, caffeine, immunoglobulin g, transcription factors, glucose tolerance test, body mass index, risk factors, life style, cell survival, gene expression regulation, genes, switch, transgenes, coffee, female, receptors, leptin, hek293 cells, synthetic biology, precision medicine
5 authors
From CH, FR
- Daniel BojarETH Zurich
- Leo SchellerETH Zurich
- Ghislaine Charpin‐El HamriInstituts Universitaires de Technologie
- Mingqi XieETH Zurich
- Martin Fussenegger · correspondingUniversity of Basel; ETH Zurich
Abstract
Programming cellular behavior using trigger-inducible gene switches is integral to synthetic biology. Although significant progress has been achieved in trigger-induced transgene expression, side-effect-free remote control of transgenes continues to challenge cell-based therapies. Here, utilizing a caffeine-binding single-domain antibody we establish a caffeine-inducible protein dimerization system, enabling synthetic transcription factors and cell-surface receptors that enable transgene expression in response to physiologically relevant concentrations of caffeine generated by routine intake of beverages such as tea and coffee. Coffee containing different caffeine concentrations dose-dependently and reversibly controlled transgene expression by designer cells with this caffeine-stimulated advanced regulators (C-STAR) system. Type-2 diabetic mice implanted with microencapsulated, C-STAR-equipped cells for caffeine-sensitive expression of glucagon-like peptide 1 showed substantially improved glucose homeostasis after coffee consumption compared to untreated mice. Biopharmaceutical production control by caffeine, which is non-toxic, inexpensive and only present in specific beverages, is expected to improve patient compliance by integrating therapy with lifestyle.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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