Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.
Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant.
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DOI：
10.1038/ncomms6392
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发表时间：
2014-11-11
影响因子：
16.6
通讯作者：
Fussenegger, Martin
中科院分区：
文献类型：
--
作者：
Folcher, Marc;Oesterle, Sabine;Zwicky, Katharina;Thekkottil, Thushara;Heymoz, Julie;Hohmann, Muriel;Christen, Matthias;El-Baba, Marie Daoud;Buchmann, Peter;Fussenegger, Martin
用于对基因表达进行无痕迹远程控制的合成设备可能会在未来的基于基因和细胞的治疗中提供新的治疗机会。在这里，我们报道了一种合成的精神控制基因开关的设计，它使人类的大脑活动和精神状态能够无线地对人类细胞中的转基因表达进行编程。一种基于脑电(EEG)的脑机接口(BCI)，用于处理特定于精神状态的脑电波，该接口对包含设计细胞的感应链接无线供电光遗传植入物进行编程，该设计细胞被设计用于近红外(NIR)光调节人类糖蛋白SEAP(分泌型碱性磷酸酶)的表达。BCI与靶基因表达的光遗传信号通路由一个工程的近红外光激活的细菌二鸟苷环化酶(DGCL)组成，该酶产生正交的第二信使环二鸟苷单磷酸(c-di-GMP)，它触发依赖于干扰素基因刺激物(STINT)的合成干扰素-β启动子的诱导。人类产生不同的精神状态(生物反馈控制、注意力集中、冥想)，可以不同地控制培养中设计细胞和小鼠皮下无线供电光遗传植入物的SEAP产生。脑机接口提供了通过大脑活动的变化来控制假肢设备的可能性。Folcher等人。将这样的系统无线连接到小鼠的光基因植入物上，以控制转基因的表达，展示了其用于精神控制药物输送的潜力。
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. Brain–machine interfaces offer the possibility of controlling prosthetic devices using changes in brain activity. Folcher et al. couple such a system wirelessly to an optogenetic implant in mice to control expression of a transgene, demonstrating its potential for mind-controlled drug delivery.
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作者：
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通讯作者：
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DOI：
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