The variable lymphocyte receptor as an antibody alternative.
The variable lymphocyte receptor as an antibody alternative.
复制标题
可变淋巴细胞受体作为抗体替代品。
DOI：
10.1016/j.copbio.2018.02.016
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发表时间：
2018
影响因子：
7.7
通讯作者：
Shusta,EricV
中科院分区：
文献类型：
--
作者：
Waters,ElizabethA;Shusta,EricV
亮点VLR 以高特异性和亲和力结合蛋白质和聚糖。七鳃鳗或盲鳗免疫可产生多种 VLR 库。VLR 支架的模块化工程成为可能。VLR 已设计用于各种治疗应用。可变淋巴细胞受体 (VLR) 是无颌脊椎动物中富含亮氨酸的重复蛋白，其功能与 Ig 抗体类似。然而，VLR 具有独特的新月形结构和模块化，导致结合界面呈凹形，与 Ig 抗体形成鲜明对比。抗原结合相互作用导致 VLR 与蛋白质和聚糖发生特异性、高亲和力结合相互作用。 VLR 的天然来源可实现免疫策略，而模块化则可实现一整套蛋白质工程方法，包括共有支架、设计的文库和利用显示技术的定向进化。 VLR 技术最近已应用于细胞特异性靶向、药物输送、肿瘤诊断甚至蛋白质稳定等领域。预计 VLR 领域将继续出现，为靶向聚糖、进化保守蛋白和细胞特异性提供独特的解决方案。
HighlightsVLRs bind proteins and glycans with high specificity and affinity.Lamprey or hagfish immunization produces diverse VLR repertoires.Modular engineering of VLR scaffolds is possible.VLRs have been engineered for a variety of therapeutic applications.Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins in jawless vertebrates that function similarly to Ig antibodies. However, VLRs possess a distinct crescent-shaped structure and modularity that results in a concave binding interface that contrasts significantly with Ig antibodies. Antigen binding interactions result in specific, high affinity VLR binding interactions with both proteins and glycans. The natural sourcing of VLRs allows for immunization strategies, while the modularity enables a whole host of protein engineering approaches including consensus scaffolds, designed libraries and directed evolution with display technologies. VLR technologies have been recently deployed for applications in cell-specific targeting, drug delivery, tumor diagnostics and even protein stabilization. It is anticipated that the VLR field will continue to emerge to provide unique solutions for targeting glycans, evolutionarily conserved proteins and cellular specificity.