| Literature DB >> 33795432 |
Robby Divine1,2, Ha V Dang1, George Ueda1,2, Jorge A Fallas1,2, Ivan Vulovic1,2, William Sheffler2, Shally Saini1,3, Yan Ting Zhao1,3,4, Infencia Xavier Raj1,3, Peter A Morawski5, Madeleine F Jennewein6, Leah J Homad6, Yu-Hsin Wan6, Marti R Tooley2, Franziska Seeger1,2, Ali Etemadi2,7, Mitchell L Fahning5, James Lazarovits1,2, Alex Roederer2, Alexandra C Walls1, Lance Stewart2, Mohammadali Mazloomi7, Neil P King1,2, Daniel J Campbell5, Andrew T McGuire6,8, Leonidas Stamatatos6,8, Hannele Ruohola-Baker1,3, Julie Mathieu3,9, David Veesler1, David Baker10,2,11.
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.Entities:
Mesh：
Substances：
Year: 2021 PMID： 33795432 PMCID： PMC8592034 DOI： 10.1126/science.abd9994
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728