Programming synthetic cells as new therapeutic vectors

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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.