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   <subfield code="a">10.1038/ncomms6392</subfield>
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   <subfield code="a">Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant</subfield>
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   <subfield code="c">[Marc Folcher, Sabine Oesterle, Katharina Zwicky, Thushara Thekkottil, Julie Heymoz, Muriel Hohmann, Matthias Christen, Marie D. El-Baba, Peter Buchmann, Martin Fussenegger]</subfield>
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   <subfield code="a">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.</subfield>
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