Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.

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.

• Authors: Marc Folcher, Sabine Oesterle, Katharina Zwicky, Thushara Thekkottil, Julie Heymoz, Muriel Hohmann, Matthias Christen, Marie Daoud El-Baba, Peter Buchmann, Martin Fussenegger
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 5392 (Nov 11 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25386727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• bis(3',5')-cyclic diguanylic acid
• Alkaline Phosphatase
• Cyclic GMP

Topics

• Alkaline Phosphatase (biosynthesis)
• Animals
• Brain-Computer Interfaces
• Cyclic GMP (analogs & derivatives, metabolism)
• Electroencephalography
• Female
• Gene Expression
• Humans
• Implants, Experimental
• Mice
• Optogenetics (methods)
• Signal Transduction
• Transcription, Genetic
• Transgenes
• Wireless Technology