The rise in the development and approval of biotherapeutics has led to a raft of new challenges requiring solutions. One of these is the aggregation that can occur during the production of biopharmaceuticals at the volumes and concentrations required for drug development and therapeutic dosing. As a consequence, tools to understand, predict and prevent protein aggregation are required.
Researchers at Leeds have formed an interdisciplinary team who use a broad range of skills and expertise to study molecular mechanisms of the aggregation process. Combining experimental & computational approaches to investigate, predict & control properties of biological molecules, the group can apply a distinctive array of techniques to an aggregation problem. For more detail on the techniques employed see here.
We have worked with the group to forge links with companies in the biopharmaceutical sector. Partnerships are being built through a series of meetings, and the development of collaborative research projects. One project already approved is a bio-processing research industry club (BRIC) CASE studentship with UCB which will investigate the binding interface(s) that trigger aggregation. We supported application for an internal proof-of-concept project which leveraged significant investment from a large biopharmaceutical partner. The project will use a series of novel flow devices to provide a simulated environment where proteins are exposed to the stresses and surface interactions they encounter during industrial scale manufacture. The effects of these stresses on the structure and dynamics of therapeutics will be measured in situ. In addition, an in vivo screen for ‘bio-processable’ candidate proteins, is being progressed with BBSRC and Innovate_UK Industrial Biotechnology catalyst funding alongside industrial partners Avacta and Medimmune.