Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.
Open accessAbstract
Synthetic devices for traceless remote control of gene expression may provide new treatment opportunities in future gene- and cell-based therapies. Here we report the design of a synthetic mind-controlled gene switch that enables human brain activities and mental states to wirelessly programme the transgene expression in human cells. An electroencephalography (EEG)-based brain–computer interface (BCI) processing mental state-specific brain waves programs an inductively linked wireless-powered optogenetic implant containing designer cells engineered for near-infrared (NIR) light-adjustable expression of the human glycoprotein SEAP (secreted alkaline phosphatase). The synthetic optogenetic signalling pathway interfacing the BCI with target gene expression consists of an engineered NIR light-activated bacterial diguanylate cyclase (DGCL) producing the orthogonal second messenger cyclic diguanosine monophosphate (c-di-GMP), which triggers the stimulator of interferon genes (STING)-dependent induction of synthetic interferon-β promoters. Humans generating different mental states (biofeedback control, concentration, meditation) can differentially control SEAP production of the designer cells in culture and of subcutaneous wireless-powered optogenetic implants in mice.
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Human brains have been connected to cell cultures, experimentally demonstrating that brain activity can control gene expression using an EEG-based BMI to trigger optogenetic stimulation of designer cells.
“Human brains have also been connected to cell cultures, experimentally demonstrating that brain activity can control gene expression, using an EEG-based BMI to trigger optogenetic stimulation of designer cells, thereby mediating their genetic expression (Folcher et al., 2014).”
From Human Brain/Cloud Interface (2019) · cites this paper as Folcher et al., 2014
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- Authors
- Folcher, M., Oesterle, S., Zwicky, K., Thekkottil, T., Heymoz, J., Hohmann, M., Christen, M., Daoud El-Baba, M., Buchmann, P., & Fussenegger, M.
- Affiliations
- ETH Zurich (CH)
- University of Basel (CH)
- Corresponding author
- Fussenegger, Martin
- Venue
- Nature Communications
- Published
- 2014-11-11
- Volume
- 5
- Issue
- 1
- Pages
- 5392-5392
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4241983
- OpenAlex
- W2149980881
- Cited by
- 130
- References
- 63
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 15 · 2020: 6 · 2019: 7 · 2018: 13 · 2017: 20 · 2016: 20 · 2015: 21 · 2014: 2
- FWCI
- 9.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- ETH Zürich Research Collection (cc-by)
- Funders
- Interreg
- FP7 Ideas: European Research Council (321381)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- optogenetics, brain-computer interface, EEG, diguanylate cyclase, c-di-GMP, STING, interferon-beta promoter, secreted alkaline phosphatase, biofeedback, meditation, concentration
- MeSH terms
- Alkaline Phosphatase, Animals, Electroencephalography, Female, Cyclic GMP, Humans, Transcription, Genetic, Signal Transduction, Gene Expression, Transgenes, Implants, Experimental, Mice, Wireless Technology, Brain-Computer Interfaces, Optogenetics
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