Development of DNA nanotechnology for chemotactic artificial cells

自下而上合成生物学的核心目标之一是生产人工细胞：由基本分子组分制备的构建体，模拟生物细胞的一种或多种功能。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递送、生化合成和生物传感等领域具有广泛的前景。重要的是，人工细胞具有用于响应疾病相关分子刺激的治疗剂的体内产生和释放的潜力。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。短程靶向可以通过用特异性结合在患病组织中过表达的受体的配体功能化人工细胞的表面来实现。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，即能够在一定距离内检测到目标的存在并向其移动。为了实现这种反应，人工细胞需要能够执行主动运动，理想情况下是沿着化学梯度（趋化性）。这种能力将是特别期望的，因为化学梯度通常由患病区域中的高浓度的特定分析物产生，例如作为炎症反应的一部分。在这个项目中，我们将结合联合收割机DNA纳米技术，微流体和理论建模，开发通用策略，实现人工细胞的运动性。该技术有可能用于治疗背景下，用于药物递送载体到其靶位点的主动运动，以及通过“通过构建理解”方法揭示基本细胞生物学。

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.