Alam Md Kausar, Gonzalez Carolina, Hill Wayne, El-Sayed Ayman, Fonge Humphrey, Barreto Kris, Geyer C Ronald
Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.
Medical Imaging, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.
Chembiochem. 2017 Nov 16;18(22):2217-2221. doi: 10.1002/cbic.201700411. Epub 2017 Oct 12.
Efforts to engineer recombinant antibodies for specific diagnostic and therapy applications are time consuming and expensive, as each new recombinant antibody needs to be optimized for expression, stability, bio-distribution, and pharmacokinetics. We have developed a new way to construct recombinant antibody-like "devices" by using a bottom-up approach to build them from well-behaved discrete recombinant antibody domains or "parts". Studies on antibody structure and function have identified antibody constant and variable domains with specific functions that can be expressed in isolation. We used the SpyTag/SpyCatcher protein ligase to join these parts together, thereby creating devices with desired properties based on summed properties of parts and in configurations that cannot be obtained by using genetic engineering. This strategy will create optimized recombinant antibody devices at reduced costs and with shortened development times.
为特定诊断和治疗应用设计重组抗体的工作既耗时又昂贵，因为每种新的重组抗体都需要在表达、稳定性、生物分布和药代动力学方面进行优化。我们开发了一种新方法，通过自下而上的方式，从表现良好的离散重组抗体结构域或“部件”构建重组抗体样“装置”。对抗体结构和功能的研究已经确定了具有特定功能的抗体恒定区和可变区，这些区域可以单独表达。我们使用SpyTag/SpyCatcher蛋白连接酶将这些部件连接在一起，从而基于部件的综合特性并以基因工程无法获得的构型创建具有所需特性的装置。这种策略将以降低的成本和缩短的开发时间创建优化的重组抗体装置。
