Science (American Association for the Advancement of Science), 2021-04, Vol.372 (6537), p.47
- Divine, Robby
- Dang, Ha V
- Ueda, George
- Fallas, Jorge A
- Vulovic, Ivan
- Sheffler, William
- Saini, Shally
- Zhao, Yan Ting
- Raj, Infencia Xavier
- Morawski, Peter A
- Jennewein, Madeleine F
- Homad, Leah J
- Wan, Yu-Hsin
- Tooley, Marti R
- Seeger, Franziska
- Etemadi, Ali
- Fahning, Mitchell L
- Lazarovits, James
- Roederer, Alex
- Walls, Alexandra C
- Stewart, Lance
- Mazloomi, Mohammadali
- King, Neil P
- Campbell, Daniel J
- McGuire, Andrew T
- Stamatatos, Leonidas
- Ruohola-Baker, Hannele
- Mathieu, Julie
- Veesler, David
- Baker, David
2021
Details
- Autor(en) / Beteiligte
- Divine, Robby
- Dang, Ha V
- Ueda, George
- Fallas, Jorge A
- Vulovic, Ivan
- Sheffler, William
- Saini, Shally
- Zhao, Yan Ting
- Raj, Infencia Xavier
- Morawski, Peter A
- Jennewein, Madeleine F
- Homad, Leah J
- Wan, Yu-Hsin
- Tooley, Marti R
- Seeger, Franziska
- Etemadi, Ali
- Fahning, Mitchell L
- Lazarovits, James
- Roederer, Alex
- Walls, Alexandra C
- Stewart, Lance
- Mazloomi, Mohammadali
- King, Neil P
- Campbell, Daniel J
- McGuire, Andrew T
- Stamatatos, Leonidas
- Ruohola-Baker, Hannele
- Mathieu, Julie
- Veesler, David
- Baker, David
- Titel
- Designed proteins assemble antibodies into modular nanocages
- Ist Teil von
- Science (American Association for the Advancement of Science), 2021-04, Vol.372 (6537), p.47
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.abd9994Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8592034
- Format
- –
- Schlagworte
- ACE2, Angiogenesis, Angiopoietin, Angiopoietins - chemistry, Angiopoietins - immunology, Angiopoietins - metabolism, Angiotensin, Angiotensin-converting enzyme 2, Antibodies, Antibodies - chemistry, Antibodies - immunology, Antibodies, Monoclonal - chemistry, Antibodies, Monoclonal - immunology, Antibodies, Neutralizing - chemistry, Antibodies, Neutralizing - immunology, Antibodies, Viral - chemistry, Antibodies, Viral - immunology, Apoptosis, Assemblies, Assembling, Assembly, Axes (reference lines), B-Lymphocytes - immunology, Binding, Biological activity, Biological products, Cages, CD40 antigen, CD40 Antigens - chemistry, CD40 Antigens - immunology, CD40 Antigens - metabolism, Cell activation, Cell culture, Cell growth, Cell Line, Tumor, Cell Proliferation, Cell surface, Clustering, Computer applications, Computer Simulation, Coronaviridae, Coronaviruses, Cyclic oligomers, Design, Domains, Electron microscopy, Fc receptors, Genes, Synthetic, Humans, Icosahedral phase, Immunoglobulin Fc Fragments - chemistry, Ligands, Lymphocyte Activation, Lymphocytes, Lymphocytes T, Mathematical models, Medicine, Models, Molecular, Monoclonal antibodies, Nanostructures, Neutralization, Oligomers, Peptidyl-dipeptidase A, Polymers, Protein A, Protein Binding, Protein Engineering, Proteins, Receptor, TIE-2 - metabolism, Receptors, Receptors, TNF-Related Apoptosis-Inducing Ligand - immunology, Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism, Respiratory diseases, SARS-CoV-2 - immunology, Severe acute respiratory syndrome, Severe acute respiratory syndrome coronavirus 2, Signal Transduction, Spike protein, Symmetry, T-Lymphocytes - immunology, T-Lymphocytes - physiology, Tumor cell lines, Valency, Viral antibodies, Viral diseases, Viruses