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Nature Medicine:远程调控遗传编码应用于调控血糖

摘要 : 为了阐明生理活动的过程,时序性调节基因表达和细胞功能的工具是极其珍贵的,甚至具有一定的临床治疗应用前景。最近一篇研究论文报道了一种新型的通过低频无线电波或磁场远程遥控的遗传编码系统。

 为了阐明生理活动的过程,时序性调节基因表达和细胞功能的工具是极其珍贵的,甚至具有一定的临床治疗应用前景。最近一篇研究论文报道了一种新型的通过低频无线电波或磁场远程遥控的遗传编码系统。

首先利用绿色荧光蛋白标记的铁蛋白的重链和轻链融合,在细胞胞内部形成以氧化铁为核心的铁蛋白纳米颗粒。那么这个铁蛋白纳米颗粒能够与抗绿色荧光蛋白-瞬时受体电位香草酸1相互作用形成融合蛋白(aGFP-TRPV1)。现有的知识表明瞬时受体电位香草酸1(TRPV1)是一种温度敏感型离子通道,温度上升时可以开启。所以当上述融合蛋白形成后,内含其中的氧化铁接收到非侵入性无线电波或磁场信号,开始产生热量,进而将离子通道激活开启。

研究者们通过细胞实验和小鼠实验均证明在氧化铁的帮助下,TRPV1的确具有转导这些力场信号的能力。离子通道的开启则引发了钙离子依赖的基因转录激活。利用干细胞或病毒表达系统将这种编码了胰岛素基因的遗传组件转入小鼠体内,通过无线电波或磁场发射信号,成功的启动了胰岛素基因的转录表达,并相应的降低了小鼠的血糖水平。

最终这种强效的可重复的体内远程调控手段也许能被应用于基础科研、工程研究以及临床治疗中,为人类创造福祉。

原文标题:Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles

Sarah A Stanley, Jeremy Sauer, Ravi S Kane, Jonathan S Dordick & Jeffrey M Friedman

Means for temporally regulating gene expression and cellular activity are invaluable for elucidating underlying physiological processes and would have therapeutic implications. Here we report the development of a genetically encoded system for remote regulation of gene expression by low-frequency radio waves (RFs) or a magnetic field. Iron oxide nanoparticles are synthesized intracellularly as a GFP-tagged ferritin heavy and light chain fusion. The ferritin nanoparticles associate with a camelid anti-GFP-transient receptor potential vanilloid 1 fusion protein, aGFP-TRPV1, and can transduce noninvasive RF or magnetic fields into channel activation, also showing that TRPV1 can transduce a mechanical stimulus. This, in turn, initiates calcium-dependent transgene expression. In mice with stem cell or viral expression of these genetically encoded components, remote stimulation of insulin transgene expression with RF or a magnet lowers blood glucose. This robust, repeatable method for remote regulation in vivo may ultimately have applications in basic science, technology and therapeutics.

来源: Nature Medicine 浏览次数:47

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