Wednesday, November 12, 2014

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

Today I would like to discuss something about a new invention happened in the research field. Just imagine the world where we can control anything with our mind. Yes that is true that there are gadget in developmental stage, by which we can control other devices just by our 'brain waves' or in simple word 'by our thought'. But we crossed the limits by developing something new, by which we can control gene expressions by though- brain waves.

Schematic representation of mind-controlled transgene expression.
Schematic representation of mind-controlled transgene expression.

Future Treatment Technique For arthritis, Diabetes, Obesity

Mammalian synthetic biology has significantly advanced the design of gene switches that are responsive to trace less cues such as light, gas and radio waves, complex gene circuits, including oscillators, cancer-killing gene classifiers and programmable biocomputers, as well as prosthetic gene networks that provide treatment strategies for gouty arthritis, diabetes and obesity. Akin to synthetic biology promoting prosthetic gene networks for the treatment of metabolic disorders cybernetics advances the design of functional man–machine interfaces in which brain–computer interfaces (BCI) process brain waves to control electromechanical prostheses, such as bionic extremities and even wheel chairs. The advent of synthetic optogenetic devices that use power-controlled, light-adjustable therapeutic interventions 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.

Future Of Gene And Cell Based Treatments using optogenetic 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-βpromoters. 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.

Optogenetic devices operating in the near-infrared (NIR) spectral range combine high tissue penetration power with negligible phototoxicity. The phototrophic bacterium Rhodobacter sphaeroides is able to capture NIR light with the multidomain protein ​BphG1, which contains an amino-terminal (N-terminal) NIR light sensor and carboxyl-terminal diguanylate cyclase (DGC) domain, as well as phosphodiesterase (PDE) activities, to control the level of the ubiquitous bacterial second messenger ​cyclic diguanosine monophosphate (​c-di-GMP) and orchestrate the environmental light-triggered transition from motile cells to biofilm-forming communities. ​Stimulator of interferon genes (​STING) was recently identified as a novel player in the human innate immunity that functions as a cyclic di-nucleotide sensor (​cGAMP, ​c-di-AMP, ​c-di-GMP) to detect the presence of cytosolic DNA via ​cyclic-GMP–AMP (cGAMP) synthase (​cGAS)-mediated production of ​cGAMP, as well as second messengers (​c-di-AMP, ​c-di-GMP) released from intracellular pathogens. Activated ​STING specifies the phosphorylation of the ​interferon-regulatory factor 3 (​IRF3) by ​tank-binding kinase 1, which results in the nuclear translocation of ​IRF3, binding to ​IRF3-specific operators and induction of type I interferon promoters. In this study, we rewire BCI-triggered NIR light-based induction of ​c-di-GMP production by ​BphG1 variants to ​c-di-GMP-dependent ​STING-driven activation of optimized interferon-responsive promoters to enable mind-controlled transgene expression in mammalian designer cells inside subcutaneous wireless-powered optogenetic implants in mice. Cybernetic control of synthetic gene networks in designer mammalian cells may pave the way for mind-genetic interfaces in future treatment strategies.

Wireless-powered optogenetic implant

The wireless-powered optogenetic implant was a fully sealed, all-in-one biocompatible device comprising a power receiver, which was remotely powered by electromagnetic induction controlled by the field generator, and the 700-nm NIR LED (λmax=700 nm, 20 mW sr−1; cat. no. ELD-700-524-1; Roithner Lasertechnik, Vienna, Austria), which enabled light-programmable transgene expression of designer cells inside the semi-permeable cultivation chamber (Fig. a–c). The power receiver’s antenna was assembled from three orthogonal copper coils (0.1-mm copper wire with 130 windings on a 7 × 7 × 7 mm ferrite cube), three in-series resonance capacitors and six Schottky diodes, which integrated and rectified the current of the three coils and powered the NIR LED in an orientation- and motion-independent manner ( Fig. b) The entire power receiver, including the base of the NIR LED, was moulded into a spherical polycarbonate cap containing polydimethylsiloxane (PDMS; cat. no. 701912-1, Sigma-Aldrich, Buchs, Switzerland) and fitted to a custom-adapted 500-μl polycarbonate chamber (0.4 × 0.9 mm) with semi-permeable polyethersulfone <300 kDa-cutoff membranes (PES Membrane, VS0651, Sartorius Stedim Biotech, Germany) on two sides (Fig. a). The device was sealed by polymerizing the PDMS for 30 min at 50 °C. The coupling intensity of the wireless-powered optogenetic implant was profiled in the space above the field generator by scoring the wireless transmission of power to the implant . A total of 500 μl of a pSO3/pSO4- or pSO3/pSBC-2 (negative control)-transgenic HEK-293F cell suspension (1 × 106cells) was loaded via a syringe through a hole in the polycarbonate side of the culture chamber, which was sealed with a PDMS plug before implanting the device subcutaneously into the mouse.
 Wireless-powered optogenetic implant.
Wireless-powered optogenetic implant.
(a) Wireless-powered implant on the field generator with an illuminated NIR LED. A 1 CHF coin (23 mm in diameter) serves as a size indicator. The 0.5-ml cultivation chamber containing semi-permeable PES membranes on both sides was moulded to a spherical polycarbonate cap contain a PDMS-sealed three-dimensional (3D) receiver antenna wired to the NIR-LED. (b) 3D receiver antenna wired via the receiver circuit (receiver coils, resonance capacitors, Schottky diodes; Supplementary Figs 5 and 11) to the NIR LED. (c) Quality-control test of the custom-made wireless-powered optogenetic implants illuminated while standing on the powered field generator. (d) Mouse with a subcutaneous wireless-powered optogenetic implant, the activity of which can be observed through the skin. (e) Field generator.

Mind-controlled transgene expression in mice

Cell-containing wireless-powered optogenetic implants were subcutaneously implanted on the backs of short-term ​isoflurane-anaesthetized wild-type mice (Oncins France souche 1, Charles River Laboratories, Lyon, France), and the cage containing the treated animals was placed on the field generator connected to the BCI. The human subject wearing the BCI headset conducted three different mental states, biofeedback, concentration and meditation, which were integrated (5/25/25 min) and converted to threshold (meditation-meter values 90/75/75)-dependent activation of the time-delay relay that switched the NIR LED in the wireless-powered optogenetic implant ON for defined periods of time (60 min/30 s/30 s) and induced light-triggered ​SEAP expression in the implanted cells. After 48 and 144 h, blood samples were collected retro-orbitally, and serum ​SEAPlevels were determined as described above. The implants of one treatment group were removed after ​SEAP profiling at 48 h, and the serum ​SEAP levels were quantified again 96 h after implant removal. Control mice received wireless-powered optogenetic implants containing pSO3/pSBC-2-transfected HEK-293F cells. Throughout the entire animal study, five 4-week-old female Oncin Souche 1 wild-type mice of the delivered pool were randomly allocated to the individual treatment groups. Neither samples nor animals were excluded from the study and blood-sample analysis was blinded

Controlling Gene Expression With Our Mind

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