纳米型：生物医学中的鲁棒微型蛋白粘合剂
Nanobodies: Robust miniprotein binders in biomedicine
影响因子:17.60000
分区:医学1区 Top / 药学1区
发表日期:2023 Apr
作者:
Jeffrey Yong Joon Kim, Zhe Sang, Yufei Xiang, Zhuolun Shen, Yi Shi
摘要
重链抗体（VHH）的可变结构域，也称为纳米体（NBS），是源自骆驼型重链纯抗体的单体抗原结合域。 NB的特征是小尺寸，高目标选择性以及明显的溶解度和稳定性，这些溶解度和稳定性共同促进了高质量的药物发展。另外，NB很容易从各种表达系统（包括大肠杆菌和酵母细胞）中表达。由于这些原因，NB已成为用于蛋白质工程，疾病诊断和治疗的首选抗体片段。迄今为止，美国食品药品监督管理局（FDA）已批准了两种基于NB的疗法。跨越临床前和临床研究，许多跨越癌症，免疫疾病，传染病和神经退行性疾病等疾病的候选人都在临床前和临床研究中。在这里，我们讨论了NB的结构特征，该特征允许特定，多功能和强大的目标结合。我们还总结了新兴技术，以识别NBS的识别，结构分析和人性化。我们的主要重点是回顾使用NBs作为模块化支架的最新进展，以促进多价聚合物用于尖端应用的工程。最后，我们讨论了NB开发的剩余挑战，并设想了基于NB的研究中的新机会。
Abstract
Variable domains of heavy chain-only antibodies (VHH), also known as nanobodies (Nbs), are monomeric antigen-binding domains derived from the camelid heavy chain-only antibodies. Nbs are characterized by small size, high target selectivity, and marked solubility and stability, which collectively facilitate high-quality drug development. In addition, Nbs are readily expressed from various expression systems, including E. coli and yeast cells. For these reasons, Nbs have emerged as preferred antibody fragments for protein engineering, disease diagnosis, and treatment. To date, two Nb-based therapies have been approved by the U.S. Food and Drug Administration (FDA). Numerous candidates spanning a wide spectrum of diseases such as cancer, immune disorders, infectious diseases, and neurodegenerative disorders are under preclinical and clinical investigation. Here, we discuss the structural features of Nbs that allow for specific, versatile, and strong target binding. We also summarize emerging technologies for identification, structural analysis, and humanization of Nbs. Our main focus is to review recent advances in using Nbs as a modular scaffold to facilitate the engineering of multivalent polymers for cutting-edge applications. Finally, we discuss remaining challenges for Nb development and envision new opportunities in Nb-based research.