Compartmentalised biomembranes as novel vaccine technologies

开发具有针对性、有效性和可编程性的新疫苗技术越来越被认为是化学生物学领域的关键工业挑战之一。将基于蛋白质和RNA的疫苗包装在脂质结合隔室内目前处于活性剂的更有效递送模式的方法的最前沿。大多数疫苗递送载体具有共同的结构基序，即由脂质层包裹的单个隔室;这种结构多样性的缺乏阻碍了它们的技术潜力。我们从生物学中知道，化学微系统复杂性的阶跃变化可以通过具有非均匀的空间组织来实现;这是通过在离散的空间位置中划分内容来实现的。在该项目中，将使用新型微流体技术开发新型疫苗递送载体，其中大小，膜组成，封装的货物和隔室数量可以根据需要“拨号”。为此，学生将开发底层微流体平台，用于使用分子组装线逐层组装一套脂质膜基序。将探索这些结构在不同隔室中容纳抗原和佐剂的能力，以及它们用于疫苗有效载荷的多阶段释放的潜力。

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.