HIGH RESOLUTION LARGE SCALE PURIFICATION OF OLIGOS

建议用于第一阶段资助的研究将在初步基础上扩大 BioWest的发现证明了置换的可行性 药用级产品的层析模式 寡核苷酸。在某些情况下，高效液相色谱法是唯一的大规模过程 产生人类治疗所需的纯度水平的步骤。 置换模式是在类似于以下条件下执行的 传统的高效液相色谱操作，而不是洗脱液中的梯度 强度进料组件从柱子上移位 精心选择的解决方案包含更强大的组件 比任何饲料成分都能被吸收。浓度和色谱柱 这种层析模式下的载药量通常为十到一百 比洗脱层析法的倍数高，因此置换更多 充分利用塔和设备的能力。这些因素， 与简化的控制方面一起，使位移 层析是一个很有希望的制造步骤。为了做出一个 商业上可行的工艺步骤，第一阶段计划的研究是 开发移位器和操作程序，以演示 寡核苷酸的提纯。本研究的目的是 在发现适合于寡核苷酸纯化的置换子时 并将技术从试验台转移到 制造环境。

The research proposed for Phase I funding will expand on preliminary findings at BioWest that demonstrate the feasibility of the displacement mode of chromatography for the production of pharmaceutical grade oligonucleotides. In certain cases, HPLC is the only large-scale process step that yields the purity levels required for human therapeutic use. The displacement mode is performed under conditions similar to conventional HPLC operations, but instead of a gradient in eluent strength the feed components are displaced from the column by a carefully chosen solution containing a component that is more strongly absorbed than any of the feed components. Concentrations and column loadings in this mode of chromatography are typically ten to one hundred fold higher than in elution chromatography, and so displacement more fully exploits the column and equipment capacity. These factors, together with simplified control aspects, make displacement chromatography a promising manufacturing step. In order to make a commercially viable process step, the research planned for Phase I is to develop displacers and operating procedures to demonstrate the purification of oligonucleotides. The motive goal of this research aims at discovering displacers appropriate to purification of oligonucleotide products and transferring the technique from the bench to the manufacturing setting.