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Designed proteins assemble antibodies into modular nanocages.
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.
Affiliation
  • Divine R; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Dang HV; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Ueda G; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fallas JA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Vulovic I; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Sheffler W; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Saini S; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Zhao YT; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Raj IX; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Morawski PA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Jennewein MF; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Homad LJ; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
  • Wan YH; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Tooley MR; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
  • Seeger F; Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA 98195, USA.
  • Etemadi A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fahning ML; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
  • Lazarovits J; Benaroya Research Institute, Seattle, WA 98101, USA.
  • Roederer A; Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.
  • Walls AC; Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.
  • Stewart L; Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.
  • Mazloomi M; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • King NP; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Campbell DJ; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • McGuire AT; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Stamatatos L; Medical Biotechnology Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
  • Ruohola-Baker H; Benaroya Research Institute, Seattle, WA 98101, USA.
  • Mathieu J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Veesler D; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Baker D; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Science ; 372(6537)2021 04 02.
Article in En | MEDLINE | ID: mdl-33795432
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.
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Full text: 1 Database: MEDLINE Main subject: Protein Engineering / Signal Transduction / Nanostructures / Antibodies Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2021 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Protein Engineering / Signal Transduction / Nanostructures / Antibodies Type of study: Prognostic_studies Limits: Humans Language: En Journal: Science Year: 2021 Type: Article Affiliation country: United States