SBIR Phase I: Removing the Purification Bottleneck in Biopharmaceutical Production

这项小企业创新研究（SBIR）项目的更广泛影响/商业潜力是开发蛋白质纯化技术，通过消除生物制药生产中的纯化瓶颈，并利用蛋白质工程和基因编辑方面的创新突破，为生物和生命科学应用提供廉价、纯化的蛋白质。这项技术的大规模推广将改变生物制药的大规模纯化，降低处方药成本——这是导致医疗成本上升的最重要因素。影响医疗保健成本上升的主要因素是药品成本的飙升——到2025年，药品将占医疗计划成本的40%。处方药成本是医疗保健中增长最快的部分，并导致医疗保健成本急剧增加。为了解决这一问题，世界范围内的制药和生物技术的重点是生物制药的开发和生产。该项目的直接效益包括成本低，使用绿色试剂，纯化蛋白中不含重金属杂质。此外，利用这种技术开发固定化酶将在生物催化、生物传感器、诊断和蛋白质输送方面开辟新的领域。该SBIR一期项目拟开发用于小规模和研究规模研究的蛋白质纯化试剂盒。将这些试剂盒推向市场将使研究人员能够在更广泛的蛋白质上进一步验证该技术，为扩大生物制药生产做准备。合成生物学通过提供对疾病更好的整体分子理解，迅速开始彻底改变药物发现和设计。然而，由于从表达系统产生的数千种自然存在的蛋白质中纯化目标重组蛋白的挑战，这种潜力尚未完全实现。该项目的三个具体目标是：1)验证多种蛋白质类别和表达系统的蛋白质标签性能；2)开发从纯化蛋白质中去除蛋白质标签的低成本方法；3)开发低表达蛋白质纯化和少量蛋白质平行纯化的解决方案。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop protein purification technology that will provide access to inexpensive, purified proteins for biological and life science applications by removing the purification bottleneck in biopharmaceutical production, and leveraging the innovative breakthroughs in protein engineering and gene editing. Scale-up of this technology will transform the large-scale purification of biopharmaceuticals and lower prescription drug costs - the most important factor contributing to rising healthcare costs. The major factor influencing the rising cost of healthcare is the skyrocketing costs of pharmaceuticals - up to 40% of the medical plan cost will be drugs by 2025. Prescription drug costs are the fastest rising component of healthcare and are contributing to the dramatic increase in healthcare costs. The worldwide focus of pharmacy and biotechnology is now on biopharmaceutical development and production to address this issue. Direct benefits of this project include low-cost, use of green reagents, and the absence of heavy metal impurities in the purified protein. In addition, the development of immobilized enzymes using this technology will open new frontiers in biocatalysis, biosensors, diagnostics and protein delivery.This SBIR Phase I project proposes to develop protein purification kits for small-scale and research-scale research. Bringing these kits to market will enable researchers to further validate the technology on a broader range of proteins in preparation for scale-up for biopharmaceutical production. Synthetic biology has quickly begun to revolutionize drug discovery and design by providing a better overall molecular understanding of disease. However, this potential has yet to be fully realized due to the challenges associated with purifying the target recombinant protein from the thousands of naturally-occurring proteins produced by the expression system. The three specific aims of the project are: 1) validation of protein tag performance for multiple protein classes and expression systems, 2) development of low-cost methods for protein tag removal from purified proteins, and 3) development of solutions for the purification of low-expressing proteins and the parallel purification of small amounts of proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.