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High-performance membrane chromatography for protein purification

用于蛋白质纯化的高性能膜层析

基本信息

批准号：
7978738
负责人：
Scott M Husson
金额：
$ 32.03万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2014-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Public demand for protein therapeutics is increasing dramatically and soon will exceed the processing capacity using existing systems - the so-called 'capacity crunch'. There is enormous pressure to identify and employ a high-throughput and high-resolution recovery and purification method that will enable the cost-effective production of the projected large masses of protein therapeutics needed in the near term. This same rapid protein recovery and purification process would be of tremendous value as an analytical technology to provide highly purified proteins for basic health-related research. Membrane chromatography has emerged as a high-throughput alternative to conventional resin column chromatography for protein purification. Yet, broad implementation of membrane chromatography in initial protein capture steps has been slow because membrane absorbers have had lower per volume protein binding capacities than resin columns. One objective of this research program is to turn high capacity into an advantage for membranes by grafting high-capacity polymer nanolayers from base membrane supports. A goal is to understand the roles of nanolayer structure, membrane pore structure, and novel polymer chemistry on protein binding, with the major objective to accelerate the use of membrane chromatography in initial protein capture steps, whether these are based on cation exchange or affinity interactions. Protein capture steps often employ affinity separation media. When the affinity ligand is a protein, the separation media becomes a major cost center for the entire purification process. Thus, low-cost synthetic affinity ligands have tremendous potential to lower purification costs for protein therapeutics produced by cell culture technology, both at the laboratory scale and at large scale. A second major objective of this research program is to use synthetic polymer chemistry to prepare high-selectivity, high-productivity affinity membranes. A modular design approach will be used to prepare affinity membranes for protein-specific purifications. Emphasis will be given to the development of affinity membranes for the isolation and purification of cell- penetrating proteins used for facilitated intracellular delivery of therapeutic agents. PUBLIC HEALTH RELEVANCE: This research program will deliver high-performance membranes for chromatography based protein purifications. The rapidly growing public demand for protein therapeutic products requires new, higher productivity, higher resolution methods for their recovery and purification. Development of these materials is essential to the production of lower cost therapeutic products for improved public health, as well as the isolation and purification of cell-penetrating proteins for facilitated intracellular delivery of therapeutic agents.

描述(申请人提供)：公众对蛋白质疗法的需求正在急剧增加，很快就会超过现有系统的处理能力--所谓的“能力紧缩”。确定和采用高通量和高分辨率的回收和纯化方法是一个巨大的压力，这种方法将能够以成本效益的方式生产预计在短期内需要的大量蛋白质疗法。这种同样快速的蛋白质回收和纯化过程作为一种分析技术将具有巨大的价值，可以为基础健康相关研究提供高度纯化的蛋白质。膜层析作为传统树脂柱层析分离蛋白质的一种高通量替代方法已经出现。然而，膜层析在最初的蛋白质捕获步骤中的广泛实施一直是缓慢的，因为膜吸附剂的单位体积蛋白质结合能力低于树脂柱。这项研究计划的一个目标是通过从基膜支架上接枝高容量的聚合物纳米层来将高容量转化为膜的优势。一个目标是了解纳米层结构、膜孔结构和新型聚合物化学对蛋白质结合的作用，主要目的是加速膜色谱在蛋白质捕获的初始步骤中的使用，无论这些步骤是基于阳离子交换还是基于亲和作用。蛋白质捕获步骤通常使用亲和分离介质。当亲和配体是蛋白质时，分离介质成为整个纯化过程的主要成本中心。因此，低成本的合成亲和配体在降低细胞培养技术生产的蛋白质治疗药物的纯化成本方面具有巨大的潜力，无论是实验室规模还是大规模。这项研究计划的第二个主要目标是利用合成聚合物化学来制备高选择性、高生产率的亲和膜。将使用模块化设计方法来制备用于蛋白质特定纯化的亲和膜。重点是开发用于分离和纯化细胞穿透蛋白的亲和膜，用于促进治疗药物的细胞内输送。与公共健康相关：该研究计划将提供用于基于层析的蛋白质纯化的高性能膜。公众对蛋白质治疗产品的需求迅速增长，需要新的、更高生产率、更高分辨率的方法来回收和纯化蛋白质治疗产品。这些材料的开发对于生产更低成本的治疗产品以改善公众健康以及分离和纯化细胞穿透蛋白以促进治疗药物的细胞内递送至关重要。