SBIR Phase I: Novel Screen for Drug Discovery

这个小企业创新研究（SBIR）一期项目旨在利用凝胶微滴（GMD）封装技术、噬菌体展示技术和荧光激活细胞分选技术开发一种新的药物发现筛选方法。在过去的十年里，噬菌体展示已经发展成为一种识别药物发现“线索”的强大工具。具有亚纳摩尔解离常数的高亲和结合物具有最大的潜在治疗价值，但它们难以通过生物筛选分离。目前，生物筛选可有效筛选~ 108个文库，其中感兴趣的噬菌体存在~ 104个拷贝。筛选高度多样化的文库（10 9），其中感兴趣的噬菌体通常存在于10-100个拷贝中，使用这种方法是困难的。为了提高生物筛选的灵敏度，已经进行了改进，但这些改进仅限于某些噬菌体。一期研究将以10 ~ 8个人类生长激素随机文库为模型文库，探索噬菌体文库筛选的新方法。该项目的商业应用将在药物发现领域。所提出的技术将提供一种生产肽和蛋白质文库的受控方法，这些文库可用于制造和提炼用于治疗药物、疾病诊断和成像试剂的分子。

This Small Business Innovation Research (SBIR) Phase I project aims to develop a novel screen for drug discovery using gel microdrop (GMD) encapsulation technology, phage display technology and fluorescence activated cell sorting. In the last decade, phage display has evolved into a powerful tool for identifying "leads" for drug discovery. High affinity binders with sub-nanomolar dissociation constant have the greatest potential therapeutic value, however, they are difficult to isolate by biopanning. Currently, biopanning is effective at screening ~10 8 libraries in which the phage of interest is present at ~10 4 copies. Screening of highly diverse libraries (10 9 ) in which phage of interest are typically present at 10-100 copies is difficult using such a method. Improvements have been made to increase the sensitivity of biopanning, but these improvements are limited to certain phage. Using a ~10 8 human growth hormone random library as a model library, Phase I research will develop a novel approach for screening phage libraries.The commercial application of this project will be in the area of drug discovery. The proposed technology will provide a controlled means of producing peptide and protein libraries that can be used to manufacture and refine molecules for use as therapeutics, and diagnostic and imaging reagents for diseases.