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

现代医学大大延长了我们人口的寿命，但医疗保健的费用非常高，而且在过去十年里急剧上升。许多美国人正在为每月的处方药费用而苦苦挣扎。药物的生产是昂贵的，这种生产成本的很大一部分可以归因于对特定活性成分的提纯和分离。这个职业项目的目的是开发一种新的方法来纯化生物衍生的活性成分，在保持药物活性的同时提高选择性，从而降低药物纯化的成本。该项目旨在开发一种专为不稳定疗法量身定做的纯化技术，这种疗法是一种高价值的药物生物分子，在溶液中的窄范围条件(如pH或离子强度)之外迅速且不可逆转地失去活性。该项目将开发一种由外部刺激(例如光和温度)控制的单一水溶液纯化工艺，这些相对温和的刺激将保持生物分子的活性。将开发新的配体，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。新开发的配体将进行深入的表征，以进行进一步的产品优化，并最终通过从血浆和细胞培养液中纯化目标蛋白来验证该技术。使用这种简单的外部开关来触发产品的捕获和释放，与当前的设置相比，极有希望显著减少工艺足迹。使用单一的水溶液不仅能确保产品的生物活性，还能显著强化工艺。这项研究需要开发有潜力刺激其他研究领域的工具，并导致发现新颖的、智能的、材料和诊断将对子孙后代的生活质量产生积极影响。一名研究生将接受该项目的培训，一名高中教师将参与实验室工作，PI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行业互动，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.