Programming synthetic cells as new therapeutic vectors

合成细胞是由生物分子构建块组装而成的非生命实体，这些生物分子构建块模仿作为生命标志的细胞行为（决策，代谢，复制，自我修复，通信等）。目前大多数合成细胞研究背后的动机围绕着它们作为简化模型的使用，在简化的环境中研究细胞生物学。由于各种技术瓶颈，它们作为临床应用中部署的微型机器的潜力在很大程度上被忽视了：一个破坏性的疏忽。在这个项目中，我们将进行一系列开创性的可行性研究，旨在为治疗性合成细胞微器件的设计和构建解锁工程规则手册。我们将利用合成生物学工具和概念来构建具有智能逻辑电路的合成细胞，这些智能逻辑电路能够通过逻辑计算按需响应大量刺激。我们的目标是采用合理的设计策略来设计软微尺度机器，这些机器能够感知肿瘤微环境中存在的物理化学线索，并通过现场合成和释放抗癌肽来响应。开发的技术将为一类全新的智能治疗剂奠定基础。在我们的模块化方法中，传感，决策和反应将交织在一起，以创造接近活细胞疗法复杂性的合成细胞。事实上，它们是无生命的，并且是重新设计的，这给它带来了丰富的优势，这意味着这将是一种强大的新治疗方式。我们的平台将通过融合脂质体生物技术，微流体技术，基因电路设计和无细胞蛋白质表达技术来实现，从而超越传统的学科界限。克服了重新设计活细胞用于治疗的局限性，而是利用仿生合成细胞微机器的力量，将开辟生物设计中未知的前沿研究领域，并成为当前方法的一步变化。

Synthetic cells are non-living entities assembled from biomolecular building blocks that mimic the cellular behaviours that are the hallmarks of life (decision making, metabolism, replication, self-repair, communication etc). The motivation behind most current synthetic cell research revolves around their use as simplified models with which to study cell biology in simplified environments. Their potential as micromachines deployed in clinical applications, has been largely neglected due to various technological bottlenecks: a damaging oversight. In this project we will undertake a series of pioneering feasibility studies aimed at unlocking an engineering rulebook for the design and construction of therapeutic synthetic cell microdevices. We will exploit synthetic biology tools and concepts for the construction of synthetic cells with smart logic circuits able to respond to a host of stimuli on-demand via logic computation.Our aim is to adopt a rational design strategy to engineer soft microscale machines able to sense physico-chemical cues present in a tumour microenvironment and respond via the on-site synthesis and release of an anti-cancer peptide. The technologies developed will lay the foundation for an entirely novel class of smart therapeutic agents. In our modular approach, sensing, decision making, and response will be intertwined, to create synthetic cells that approach the sophistication of live-cell therapies. The fact they are non-living and designed de-novo brings it a wealth of advantages, meaning this will be a powerful new therapeutic modality. Our platforms will be enabled by fusing together liposome biotechnology, microfluidics, gene circuit design and cell free protein expression technologies, hence transcending traditional disciplinary boundaries. Bypassing the limitations of re-engineering living cells for therapeutics, and instead leveraging the power of biomimetic synthetic cells micromachines will open up unchartered frontier research areas in biodesign and be a step change on current approaches.