Optogenetic devices operating in the near-infrared (NIR) spectral range combine high tissue penetration power with negligible phototoxicity 19, 20. The advent of synthetic optogenetic devices that use power-controlled, light-adjustable therapeutic interventions 18 will enable the merging of synthetic biology with cybernetics to allow brain waves to remotely control the transgene expression and cellular behaviour in a wireless manner. Akin to synthetic biology promoting prosthetic gene networks for the treatment of metabolic disorders 1, 11, 12, 13, cybernetics advances the design of functional man–machine interfaces in which brain–computer interfaces (BCI) 14, 15 process brain waves to control electromechanical prostheses, such as bionic extremities 16 and even wheel chairs 17. Mammalian synthetic biology has significantly advanced the design of gene switches that are responsive to traceless cues such as light 1, 2, gas 3 and radio waves 4, complex gene circuits, including oscillators 5, 6, cancer-killing gene classifiers 7, 8 and programmable biocomputers 9, as well as prosthetic gene networks 10 that provide treatment strategies for gouty arthritis 11, diabetes 1, 12 and obesity 13. 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. 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.
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).
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. Synthetic devices for traceless remote control of gene expression may provide new treatment opportunities in future gene- and cell-based therapies.
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