SBIR Phase II: High-capacity membrane for fast and selective capture of mRNA

项目摘要 这一SBIR直通二期项目将开发出第一个用于纯化高表达mRNA的亲和膜 容量、选择性和吞吐量。信使核糖核酸药物有可能解决各种不同的 病理学。FDA对两种基于m RNA的新冠肺炎疫苗的紧急使用授权代表了 信使核糖核酸治疗新时代的曙光。然而，一家开创基因药物的公司透露， 缺乏高通量的纯化工艺是在扩大规模时必须解决的主要障碍 工业基因。Purilogics预计，拟议的创新的商业化将产生重大影响 高通量解决纯化难题的信使核糖核酸药物开发 在发现和工业生产规模方面经验丰富。通过将净化周期从几个小时减少到 几分钟后，这项创新将提高生产率，并通过关联改善患者获得mRNA的机会 疫苗和药物。该项目的产品将是市场上第一款，预包装的亲和膜多 可快速分离提纯In中mRNA药物的井板、色谱柱和色谱盒 体外转录混合物。由于驻留时间较长，竞争产品的生产率较低 需要提纯。此外，它们对大尺寸信使核糖核酸的容量极低。在我们最初的研究中， 证明了制备高产率的信使核糖核酸亲和膜的可行性。膜层析 柱子原型的性能大大超过了竞争对手的商业产品，而且生产率和 可重用性里程碑超过了定义的进入第二阶段的验收标准。 Collaborator使用专有的mRNA馈送流对原型进行了评估。净化速度更快， 获得了比竞争产品更高的信使核糖核酸回收率和相近的纯度。第二阶段的目标是(一) 开发容量更大的信使核糖核酸亲和性膜，以减少信使核糖核酸的纯化时间 所有大小的；(Ii)敲定可扩展的mRNA亲和性膜的工艺并开发原型，以及(Iii) 确定信使核糖核酸亲和膜柱的工作范围，并对原型进行现场研究 通过行业协作。在具体目标1中，我们将系统地评估合成所起的作用 膜条件和膜孔径对性能的影响。在具体目标2中，我们将建立一个生产过程 这些膜。我们将制作一系列膜柱、横向进料盒和多孔 膜板原型。在具体目标3中，Purilogics将与行业领导者合作评估 多尺度捕获步骤纯化mRNA的原型(研究/中试/生产)。进入中国市场 新的生物处理工具在临床第二阶段试验之前。大多数信使核糖核酸药物处于I期和II期 临床试验中，现在是开发一种高产的mRNA纯化技术的时候了。可寻址的 预计到2026年，预包装的信使核糖核酸捕获步骤层析产品的市场规模将达到2亿美元。

Project Summary This SBIR Direct to Phase II project will develop the first affinity membrane for purifying mRNA with high capacity, selectivity, and throughput. mRNA medicines have the potential to address a wide variety of pathologies. FDA emergency use authorizations for two mRNA-based COVID-19 vaccines represent the dawning of a new era of mRNA therapies. However, a company pioneering mRNA medicines has revealed that the lack of high throughput purification processes is a major hurdle that must be addressed in the upscaling of industrial mRNA. Purilogics expects that commercialization of the proposed innovation will have a major impact on the development of mRNA medicines by providing high-throughput solutions to the purification challenges experienced at the discovery and industrial production scales. By reducing purification cycles from hours to minutes, the innovation will increase productivity and, by association, improve patient accessibility to mRNA vaccines and medicines. The products of this project will be first-in-market, prepacked affinity membrane multi- well plates and chromatography columns and cassettes that can rapidly isolate and purify mRNA drugs from in vitro transcription mixture. Competing products have low productivity because of the long residence times needed for purification. In addition, their capacities are extremely low for large size mRNA. In our initial study, we proved the feasibility of fabricating high productivity mRNA affinity membranes. Membrane chromatography column prototypes dramatically outperformed competing commercial products, and the productivity and reusability milestones exceeded the defined acceptance criteria for moving to Phase II. Our industry collaborator evaluated the prototypes using proprietary mRNA feed streams. The purifications were faster and attained higher mRNA recovery and similar purity compared to competing products. The Phase II aims are (i) to develop mRNA affinity membranes with increased capacity that enable reduced purification times for mRNA of all sizes; (ii) to finalize a scalable process for mRNA affinity membranes and develop prototypes, and (iii) to determine mRNA affinity membrane column operating ranges and conduct field research on prototypes through industry collaboration. In Specific Aim 1, we will systematically evaluate the roles played by synthesis conditions and membrane pore size on performance. In Specific Aim 2, we will establish a process to produce the membranes. We will fabricate a series of membrane columns, laterally fed cassettes, and multi-well membrane plate prototypes. In Specific Aim 3, Purilogics will collaborate with an industry leader to evaluate prototypes for capture step purification of mRNA at multiple scales (research/pilot/production). Market entry for new bioprocessing tools is prior to clinical phase II trials. With the majority of mRNA drugs in phase I and II clinical trials, the time to develop a high-productivity mRNA purification technology is now. The addressable market for prepacked mRNA capture-step chromatography products is expected to reach $200 million by 2026.