STTR Phase II: Commercial Cell-Free Technology for Insulin-Like Growth Factor I (IGF-I) Production

这个小型技术转移创新研究(STTR)第二阶段项目建议开发一种无细胞工艺来生产胰岛素样生长因子I(IGF-1)。之前的第一阶段工作表明，通过仔细控制环境条件和使用的催化剂，胰岛素样生长因子-1的产量非常高(即800ug/L)。这些结果表明，无细胞生产IGF-1不仅在技术上是可行的，而且无细胞技术可能是生产任何在细菌系统中难以产生的含二硫键蛋白质的重要方法。第二阶段项目将侧重于质量控制(即产品表征和优化)、反应放大和降低成本。无细胞过程潜在地提供了高资本生产率，以及对蛋白质表达和折叠过程中存在的条件的前所未有的控制。这两个属性对于像IGF-1这样的分子来说尤其重要，这些分子旨在用于价格敏感的市场，而且既难以折叠，又受到各种有害产品修饰的影响。该项目的商业应用将在生物制药领域，用于无细胞生产重要的蛋白质药物IGF-1，并可能用于生产其他重要的治疗性蛋白质。无细胞工艺是一种低成本、快速、灵活的蛋白质制造平台，能够从开发扩大到最终制造，并将消除基于蛋白质的药物开发工作中的关键制造和生产瓶颈。

This Small Technology Transfer Innovation Research (STTR) Phase II project proposes to develop a cell-free process to produce insulin-like growth factor I (IGF-1). Prior Phase I work showed production of IGF-1 in very high yields (i.e. 800 ug/L) by a careful control of the environmental conditions and the catalysts that were used. These results show that not only the cell-free production of IGF-1 is technically feasible, but also that cell-free technology may be an important method for the production of any disulfide-containing protein that is difficult to produce in bacterial systems. The Phase II project will focus on quality control (that is, product characterization and optimization), reaction scale-up, and cost reduction. The cell-free process potentially offers high capital productivity along with unprecedented control over the conditions present during protein expression and folding. Both attributes are especially important for molecules such as IGF-1 that are intended for price-sensitive markets and that are both difficult to fold and are also subject to a variety of deleterious product modifications.The commercial application of this project will be in the area of biopharmaceuticals, for the cell-free production of an important protein drug, IGF-1, and potentially for the production of other important therapeutic proteins. The cell-free process is a low-cost, rapid, flexible protein-manufacturing platform that is capable of scaling up from development through to final manufacturing and would remove critical manufacturing and production bottlenecks in protein based drug development efforts.