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

Nat Commun. 2014 Nov 11:5:5392. doi: 10.1038/ncomms6392.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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