2021年4月2日出版的《科学》杂志发表了美国科学家的一项最新研究成果。来自华盛顿大学的David Baker小组利用设计的蛋白将抗体组装到模块化的纳米笼中。
受体结合抗体或配体的多价展示可以增强其活性。研究人员通过纳米笼的计算设计来统一了这种形式和功能，而不是通过附着到已有的支架上实现多价。电子显微镜确定了八面笼的结构，并且与相应的计算模型紧密匹配。
与游离抗体或Fc融合在死亡受体5（DR5）介导的凋亡，血管生成素1受体（Tie2）介导的血管生成，CD40活化和T细胞增殖中相比，靶向细胞表面受体的抗体纳米笼能够增强信号传导。纳米笼组装还可以通过α-SARS-CoV-2单克隆抗体和Fc-血管紧张素转换酶2（ACE2）融合蛋白来增强SARS-CoV-2假病毒的中和作用。
附：英文原文
Title: Designed proteins assemble antibodies into modular nanocages
Author: Robby Divine, Ha V. Dang, George Ueda, Jorge A. Fallas, Ivan Vulovic, William Sheffler, Shally Saini, Yan Ting Zhao, Infencia Xavier Raj, Peter A. Morawski, Madeleine F. Jennewein, Leah J. Homad, Yu-Hsin Wan, Marti R. Tooley, Franziska Seeger, Ali Etemadi, Mitchell L. Fahning, James Lazarovits, Alex Roederer, Alexandra C. Walls, Lance Stewart, Mohammadali Mazloomi, Neil P. King, Daniel J. Campbell, Andrew T. McGuire, Leonidas Stamatatos, Hannele Ruohola-Baker, Julie Mathieu, David Veesler, David Baker
Issue&Volume: 2021/04/02
Abstract: Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)–mediated apoptosis, angiopoietin-1 receptor (Tie2)–mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc–angiotensin-converting enzyme 2 (ACE2) fusion proteins.
DOI: 10.1126/science.abd9994
Source: https://science.sciencemag.org/content/372/6537/eabd9994