Compartmentalised biomembranes as novel vaccine technologies

靶向、有效和可编程的新疫苗技术的开发越来越被认为是化学生物学领域的关键工业挑战之一。在脂质结合的隔间内包装疫苗，包括基于蛋白质和基于RNA的疫苗，目前处于更有效地提供活性物质的方法的前沿。大多数疫苗运送工具都有一个共同的结构主题，即由脂层包裹的单个隔室；这种缺乏结构多样性的情况阻碍了它们的技术潜力。我们从生物学中知道，化学微系统的复杂性的阶段性变化可以通过具有非统一的空间组织来实现；这是通过将离散空间位置中的内容分区来实现的。在该项目中，将使用新的微流控技术开发新的疫苗递送工具，其中大小、膜成分、包裹的货物和隔室的数量可以按需“拨入”。为此，学生将开发底层微流控平台，使用分子装配线逐层组装一套类脂膜基元。将探索这些结构在不同隔室中容纳抗原和佐剂的能力，以及它们多阶段释放疫苗有效载荷的潜力。

The development of new vaccine technologies that are targeted, effective, and programmable is increasingly being recognised as one of the key industrial challenges in chemical biology. The packing of vaccines , both protein- and RNA-based, inside a lipid-bound compartment is currently at the forefront of approaches to a more effective delivery mode of the active agents. The majority of vaccine delivery vehicles share a common structural motif, namely that of a single compartment encased by a lipid layer; this lack of architectural diversity has hindered their technological potential. We know from biology that step changes in sophistication of chemical microsystems can be achieved by having non-uniform spatial organisation; this is achieved through compartmentalisation of content in discrete spatial locations. In this project, novel vaccine delivery vehicles will be developed using novel microfluidic technologies, where the size, membrane composition, encapsulated cargo, and number of compartments can be 'dialled-in' on demand. To do this, the student will develop underlying microfluidic platforms for the layer-by-layer assembly of a suite of lipid membrane motifs using a molecular assembly line. The ability of these structures to house both the antigen and adjuvant in different compartments will be explored, together with their potential for multi-stage release of a vaccine payload.