Cell子刊：芝加哥科学家实现光遗传学技术新突破

    随着近年来科学家在表观遗传学领域研究的深入，人们开始希望通过体外刺激的方式来控制体内细胞尤其是神经元细胞的状态。这一领域有着广阔的应用前景，如治疗黄斑病变等遗传病。以此为基础，光遗传学等学科纷纷被建立起来。不过，目前为止，为了实现这一目标，研究人员不得不对神经元进行基因改造。这也极大阻碍了这一技术的普及。

    最近来自芝加哥大学和伊利诺伊大学芝加哥分校的研究人员们在这一领域实现了突破。研究人员利用远红外光产生的热量来控制正常神经元细胞正常的生命活动。不同于以往在正常神经元细胞中表达光敏蛋白的做法，来自芝加哥的科学家们选择使用金纳米颗粒来定位特定的神经元。为了解决金纳米颗粒专一性的问题，研究人员将一种蝎神经毒素Ts1连接到金纳米颗粒上。Ts1可以通过识别神经元细胞表面的钠离子通道来靶向识别神经元细胞。这也是人类首次在不改造神经元遗传特性的基础上，实现光控神经元活动的目的。不过，这一研究仍处于早期阶段，研究人员同时表示Ts1可能对神经元细胞存在毒性。这一研究工作被发表在Neuron杂志上。

    原文链接：Photosensitivity of Neurons Enabled by Cell-Targeted Gold Nanoparticles

Unmodified neurons can be directly stimulated with light to produce action potentials, but such techniques have lacked localization of the delivered light energy. Here we show that gold nanoparticles can be conjugated to high-avidity ligands for a variety of cellular targets. once bound to a neuron, these particles transduce millisecond pulses of light into heat, which changes membrane capacitance, depolarizing the cell and eliciting action potentials. Compared to non-functionalized nanoparticles, ligand-conjugated nanoparticles highly resist convective washout and enable photothermal stimulation with lower delivered energy and resulting temperature increase. Ligands targeting three different membrane proteins were tested; all showed similar activity and washout resistance. This suggests that many types of ligands can be bound to nanoparticles, preserving ligand and nanoparticle function, and that many different cell phenotypes can be targeted by appropriate choice of ligand. The findings have applications as an alternative to optogenetics and potentially for therapies involving neuronal photostimulation.