GOALI: Understanding the effect of sequence on expression of recombinant monoclonal antibodies

0854099 Sharfstein拟议项目的智力优势是通过以下方式对基因和蛋白质序列与重组单抗表达水平之间的关系有一个基本的了解：*创建重组治疗性单抗的序列变体文库*在中国仓鼠卵巢(CHO)细胞中表达这些变体*分析mRNA水平、细胞内外抗体水平并将其表达与基因和蛋白质序列相关联*将本研究的结果与UCB Celltech(英国斯劳)以前对其他抗体的研究结果进行比较，以确定始终受蛋白质稳定性控制还是其他机制也发挥了作用。拟议工作的更广泛影响是：*为化学工程专业的女博士生提供独特的教育经验，将工业实习和可作为国内研究生国际经验典范的国际经验结合起来*为美国的生物技术和生物制药行业提供关键知识*发展伦斯勒理工学院和UCB之间的持续关系，这将在受邀的IGERT分子生物处理提案中发挥重要作用

0854099SharfsteinThe intellectual merit of the proposed project is to develop a fundamental understanding of the relationships between gene and protein sequence and expression level of recombinant monoclonal antibodies by:* Creating a library of sequence variants for a recombinant therapeutic monoclonal antibody* Expressing these variants in Chinese Hamster Ovary (CHO) cells* Analyzing the mRNA levels and intra- and extra-cellular antibody levels and correlating the expression with gene and protein sequence* Comparing the results of this study with previous studies of other antibodies performed by UCB Celltech (Slough, UK) to determine whether always controlled by protein stability or if other mechanisms also play a role. The broader impacts of the proposed work are to: * Provide a unique educational experience for a female doctoral student in Chemical Engineering, combining an industrial internship and an international experience that can serve as a model for international experiences for domestic graduate students* Provide critical knowledge to the biotechnology and biopharmaceutical industry in the United States* Develop an ongoing relationship between Rensselaer Polytechnic Institute and UCB that will play an important role in an invited IGERT proposal in molecular bioprocessing