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ABSTRACT

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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