Development of DNA nanotechnology for chemotactic artificial cells

自底向上合成生物学的核心目标之一是制造人造细胞：由模拟生物细胞的一种或多种功能的基本分子成分制备的结构。由于其行为和组成的完全可编程性，这些细胞模拟物在药物输送、生化合成和生物传感等领域具有广泛的应用前景。重要的是，人造细胞有潜力用于体内生产和释放治疗药物，以响应疾病相关的分子刺激。在这种情况下，人工细胞应该具有的一个关键能力是靶向病变细胞或组织，以减少治疗的毒性。短距离靶向可以通过使用特异性结合病变组织中过度表达的受体的配体使人造细胞表面功能化来实现。然而，DNA纳米技术的进步意味着一种更有价值的策略即将出现：远程靶向，即在远处探测目标的存在并向其移动的能力。为了实现这样的反应，人造细胞需要能够进行主动运动，理想情况下是沿着化学梯度（趋化性）运动。这种能力是特别需要的，因为化学梯度通常是由病变区域高浓度的特定分析物引起的，例如作为炎症反应的一部分。在这个项目中，我们将结合DNA纳米技术、微流体学和理论建模来制定实现人造细胞运动的一般策略。这项技术有潜力用于治疗环境，使药物输送载体主动移动到靶点，并通过“通过构建来理解”的方法揭示基本的细胞生物学。

One of the core aims of bottom-up synthetic-biology to produce artificial cells: constructs prepared from elementary molecular components that mimic one or more functionalities of biological cells. Owing to the complete programmability of their behaviour and composition, these cell mimics have widespread promise in areas such as drug delivery, biochemical synthesis, and biosensing. Importantly, artificial cells have the potential to be used for the in-vivo production and release of therapeutic agents in response to disease-related molecular stimuli. A key ability that artificial cells should have in this context is that of targeting diseased cells or tissue, in order to reduce the toxicity of the treatment. Short-range targeting can be achieved by functionalising the surface of artificial cells with ligands that specifically bind receptors overexpressed in diseased tissues. However, advances in DNA nanotechnology have meant an even more valuable strategy is on the horizon: long-range targeting, i.e. the ability to detect the presence of the target at a distance and move towards it. For such a response to be implemented, artificial cells require the ability to perform active motion, ideally along a chemical gradient (chemotaxis). This capability would be particularly desirable as chemical gradients often result from a high concentration of specific analytes in diseased areas, e.g. as part of the inflammatory response. In this project, we will combine DNA nanotechnology, microfluidics and theoretical modelling to develop general strategies to achieve motility in artificial cells. This technology has the potential to be used in a therapeutic context, for active motion of drug-delivery vehicles to their target site, as well as shedding light of fundamental cell biology through an 'understanding by building' approach.