Selection of human VH single domains with improved biophysical properties by phage display.
Selection of human VH single domains with improved biophysical properties by phage display.
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DOI：
10.1007/978-1-61779-968-6_23
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发表时间：
2012-01-01
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影响因子：
--
通讯作者：
Christ, Daniel
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文献类型：
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作者：
Dudgeon, Kip;Rouet, Romain;Christ, Daniel
人抗体可变重链（VH）结构域在分离表达时倾向于显示差的生物物理性质。因此，这些结构域通常以低表达水平、高聚集水平和增加的“粘性”为特征。“在这里，我们描述了允许通过噬菌体展示工程改造具有改善的生物物理特性的人VH结构域的方法。工程化的结构域承受挑战性的条件，如高温和酸性pH。工程化的人单结构域是一类有前途的新的抗体片段，代表了强大的研究工具和抗体治疗剂的产生的积木。
Human antibody variable heavy (VH) domains tend to display poor biophysical properties when expressed in isolation. Consequently, the domains are often characterized by low expression levels, high levels of aggregation, and increased "stickiness." Here, we describe methods that allow the engineering of human VH domains with improved biophysical properties by phage display. The engineered domains withstand challenging conditions, such as high temperature and acidic pH. Engineered human single domains are a promising new class of antibody fragments and represent robust research tools and building blocks for the generation of antibody therapeutics.