Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.
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.
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Marc
M
Folcher
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Sabine
S
Oesterle
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Katharina
K
Zwicky
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Thushara
T
Thekkottil
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Julie
J
Heymoz
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Muriel
M
Hohmann
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Matthias
M
Christen
Département Génie Biologique, Institut Universitaire de Technologie (IUTA), 74 Boulevard Niels Bohr, F-69622 Villeurbanne, France.
Marie
M
Daoud El-Baba
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Peter
P
Buchmann
1] Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland [2] Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Martin
M
Fussenegger
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D062207:Brain-Computer Interfaces; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D015870:Gene Expression; D006801:Humans; D020007:Implants, Experimental; D051379:Mice; D062308:Optogenetics / Q000379:methods*; D015398:Signal Transduction; D014158:Transcription, Genetic; D019076:Transgenes; D059015:Wireless Technology
C062025:bis(3',5')-cyclic diguanylic acid; D000469:Alkaline Phosphatase; D006152:Cyclic GMP