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Generation of human de novo pIX phage display libraries

机译:人类 de novo pIX噬菌体展示文库的生成

摘要

Described and claimed herein are combinatorial synthetic Fab libraries displayed on a phage pIX protein. The libraries were built on scaffolds representing the most frequently used genes in human antibodies, which were diversified to mirror the variability of natural antibodies. After selection using a diverse panel of proteins, numerous specific and high-affinity Fabs were isolated. By a process called in-line maturation the affinity of some antibodies was improved up to one hundred-fold yielding low pM binders suitable for in vivo use. This work thus demonstrates the feasibility of displaying complex Fab libraries as pIX-fusion proteins for antibody discovery and lays the foundations for studies on the structure-function relationship of antibodies.
机译:本文描述并要求保护的是在噬菌体pIX蛋白上展示的组合合成Fab文库。该文库建立在代表人类抗体中最常用基因的支架上,该支架被多样化以反映天然抗体的变异性。使用多种蛋白质进行选择后,分离出许多特异性和高亲和力的Fab。通过称为在线成熟的方法,一些抗体的亲和力提高了一百倍,从而产生了适合体内使用的低pM结合剂。因此,这项工作证明了展示复杂的Fab文库作为pIX融合蛋白用于抗体发现的可行性,并为研究抗体的结构-功能关系奠定了基础。

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