The rational design of artificial membrane-binding proteins for advanced cell therapies

细胞疗法为一系列疾病提供了新的和独特的解决方案。然而，细胞疗法受到它们到达目标位置、停留在那里以及在不合适的环境（如缺氧）中存活的能力的限制。增强细胞治疗绕过这些限制是一个令人兴奋的研究领域，该项目打算解决。通过工程增压蛋白，可以通过静电相互作用将其与表面活性剂结合。通过这样做，它们能够将自己固定在细胞的外膜内。虽然增压肌红蛋白（锚蛋白）提供氧气储存功能，但也可以将具有附加功能的次级蛋白偶联到锚蛋白上，以获得额外的好处，例如，归巢或信号传导。其中一种“伴侣蛋白”是程序性细胞死亡蛋白1 (PD1)，它是癌症治疗的常见障碍。该项目旨在解决细胞疗法的一些局限性，通过设计不同的锚蛋白和伴侣蛋白组装，作为可能的细胞治疗附加组件在体内进行测试。

Cell therapies offer new and unique solutions to a range of maladies. However, cell therapies are limited by their ability to reach their target locations, remain there, and survive within unsuitable environments, such as hypoxia. Augmenting cell therapies towards circumventing these limitations is an exciting area of research which this project intents to address. Through engineering supercharged proteins it is possible conjugate them to surfactants via electrostatic interactions. In doing so, they are able to anchor themselves within the outer membrane of cells. While supercharged Myoglobin (anchor protein) offers the function of oxygen storage, it is also possible to conjugate secondary proteins with added function to the anchor protein to confer additional benefits e.g., homing or signalling. One such 'partner protein' is the programmed cell death protein 1 (PD1) which is a common hindrance for cancer treatments. This project intends to tackle some of the limitations of cell therapies through engineering different assemblies of anchor and partner proteins to be tested in vivo as possible cell therapy add-ons.