Enhancing Productivity and Protein Quality in Perfusion Cultures

生物制药蛋白质的治疗效果对生产条件极为敏感，因为它们会影响翻译后修饰。因此，任何生产用于人类的这种蛋白质的新概念都需要对其对产品完整性的影响进行彻底的表征。这项拟议的研究将调查作者的假设，即与快速生长的分批培养相比，缓慢生长的灌流培养产生更多与治疗相关的糖蛋白。这项建议从推动开发一类重要的新治疗剂(即重组糖蛋白)的实际角度出发，解决了一个具有深远后果的问题。在这一领域取得成功将带来可观的经济回报。此外，从“先进知识”的角度来看，这项提案的目标之一也是更好地了解决定糖基化模式的潜在生物过程。

0541119KompalaThe therapeutic efficacy of a biopharmaceutical protein is extremely sensitive to the production conditions because they influence post-translation modifications. Therefore, any new concept for production of such proteins used in humans requires thorough characterization of its impact on the integrity of the product. The proposed study will investigate the author's hypothesis that slow growing perfusion cultures produce more therapeutically relevant glycoproteins compared to those produced in faster growing batch cultures. This proposal addresses an issue that has profound consequences from the practical perspective of advancing the development of an important new class of therapeutic agents (i.e., recombinant glycoproteins). Success in this area will have a significant financial payoff. In addition, from the perspective of "advancing knowledge" this proposal also has as one of its aims the goal of better understanding the underlying biological processes that determine glycosylation patterns.