CAREER: Light- and temperature- controlled peptide ligands for purifying blood factors and orphan enzyme drugs

现代医学大大延长了人类的寿命，但医疗保健的费用非常高，而且在过去十年中急剧上升。许多美国人都在为每月的处方药费用而挣扎。药品的生产是昂贵的，这种生产成本的很大一部分可归因于特定活性成分的纯化和分离。本CAREER项目的目的是开发一种纯化生物源性活性成分的新方法，在保持药物活性的同时增加选择性，从而降低药物纯化的成本。该项目旨在开发一种针对不稳定疗法的纯化技术，不稳定疗法是高价值的药物生物分子，在溶液的狭窄条件范围之外（如pH或离子强度）迅速且不可逆地失去其活性。该项目将开发一种由外部刺激控制的单一水溶剂净化工艺，例如光和温度，相对温和的刺激将保留生物分子的活性。新的配体将被开发出来，在可见光或环境温度下选择性地捕获两个目标生物分子，并在黑暗或寒冷中释放药物。新开发的配体将被深入表征，以便进一步优化产品，最后，通过纯化血浆和细胞培养液中的靶蛋白来验证该技术。与当前设置相比，使用这种简单的外部开关来触发产品的捕获和释放，有望大大减少流程占用空间。使用单一的含水溶剂不仅保证了产品的生物活性，而且还使显著的工艺强化。这项研究需要开发工具，这些工具有可能刺激其他研究领域，并导致发现新颖的智能方法。将对子孙后代的生活质量产生积极影响的材料和诊断。一名研究生将在该项目中接受培训，一名高中教师将参与实验室工作，项目负责人将利用他在生物制造教育和培训中心的任命，与当地生物技术产业互动，并将这项工作的知识产权商业化。

Modern medicine has drastically increased the life span of our population, yet the cost of health care is very high, and has risen drastically over the past decade. Many Americans struggle with their monthly cost for prescription drugs. The production of pharmaceuticals is expensive, and a large portion of this production cost can be attributed to purification and isolation of a particular active component. The aim of this CAREER project is to develop a new method for purification of biologically-derived active components that increases selectivity while maintaining the activity of the drug, thereby decreasing the cost of drug purification. This project is aimed towards the development of a purification technology tailored for labile therapeutics, which are high-value drug biomolecules that rapidly and irreversibly lose their activity outside a narrow range of conditions in solution (such as pH or ionic strength). The project will develop a single aqueous solvent purification process that is controlled by external stimuli, e.g. light and temperature, relatively mild stimulations that will retain the activity of the biomolecules. New ligands will be developed that selectively captures two target biomolecules under visible light, or ambient temperature, and releases the drug in dark or cold. The newly developed ligands will be characterized in depth to allow for further product optimization and finally, validation of the technique by purifying target proteins from blood plasma and cell culture fluids. The use of such simple, external switches to trigger the capture and release of the product holds great promise to considerably reduce the process footprint as compared to current setups. The use of a single aqueous solvent not only ensures product bioactivity, but also enables significant process intensification. The research entails the development of tools that have the potential to stimulate other research areas, and lead to the discovery of novel ?smart? materials and diagnostics that will have a positive impact on the quality of life of future generations. One graduate student will be trained in this project, a high school teacher will be involved in the laboratory work, and the PI will leverage his appointment in a biomanufacturing education and training center to interact with local biotech industries and commercial the intellectual property from this work.