Designed Proteins Assemble Antibodies Into Modular Nanocages

Designed Proteins Assemble Antibodies Into Modular Nanocages Publisher Pubmed

Divine R^{1, 2} ; Dang HV¹ ; Ueda G^{1, 2} ; Fallas JA^{1, 2} ; Vulovic I^{1, 2} ; Sheffler W² ; Saini S^{1, 3} ; Zhao YT^{1, 3, 4} ; Raj IX^{1, 3} ; Morawski PA⁵ ; Jennewein MF⁶ ; Homad LJ⁶ ; Wan YH⁶ ; Tooley MR² Show All Authors

Divine R^{1, 2}
Dang HV¹
Ueda G^{1, 2}
Fallas JA^{1, 2}
Vulovic I^{1, 2}
Sheffler W²
Saini S^{1, 3}
Zhao YT^{1, 3, 4}
Raj IX^{1, 3}
Morawski PA⁵
Jennewein MF⁶
Homad LJ⁶
Wan YH⁶
Tooley MR²
Seeger F^{1, 2}
Etemadi A^{2, 7}
Fahning ML⁵
Lazarovits J^{1, 2}
Roederer A²
Walls AC¹
Stewart L²
Mazloomi M⁷
King NP^{1, 2}
Campbell DJ⁵
Mcguire AT^{6, 8}
Stamatatos L^{6, 8}
Ruoholabaker H^{1, 3}
Mathieu J^{3, 9}
Veesler D¹
Baker D^{1, 2, 10}

Show Affiliations

1. Department of Biochemistry, University of Washington, Seattle, 98195, WA, United States
2. Institute for Protein Design, University of Washington, Seattle, 98195, WA, United States
3. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, 98109, WA, United States
4. Oral Health Sciences, School of Dentistry, University of Washington, Seattle, 98195, WA, United States
5. Benaroya Research Institute, Seattle, 98101, WA, United States
6. Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, 98019, WA, United States
7. Medical Biotechnology Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
8. Department of Global Health, University of Washington, Seattle, 98195, WA, United States
9. Department of Comparative Medicine, University of Washington, Seattle, 98195, WA, United States
10. Howard Hughes Medical Institute, University of Washington, Seattle, 98195, WA, United States

Source: Science Published:2021

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 a-SARS-CoV-2 monoclonal antibodies and Fc-angiotensinconverting enzyme 2 (ACE2) fusion proteins. © 2021 American Association for the Advancement of Science. All rights reserved.

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Style	Citing Format
MLA	Divine R, et al.. "Designed Proteins Assemble Antibodies Into Modular Nanocages." Science, vol. 372, no. 6537, 2021, pp. -.
APA	Divine R, Dang HV, Ueda G, Fallas JA, Vulovic I, Sheffler W, Saini S, Zhao YT, Raj IX, Morawski PA, Jennewein MF, Homad LJ, Wan YH, Tooley MR, Seeger F, Etemadi A, Fahning ML, Lazarovits J, Roederer A, ... Baker D (2021). Designed Proteins Assemble Antibodies Into Modular Nanocages. Science, 372(6537), -.
Chicago	Divine R, Dang HV, Ueda G, Fallas JA, Vulovic I, Sheffler W, Saini S, et al.. "Designed Proteins Assemble Antibodies Into Modular Nanocages." Science 372, no. 6537 (2021): -.
Harvard	Divine R et al. (2021) 'Designed Proteins Assemble Antibodies Into Modular Nanocages', Science, 372(6537), pp. -.
Vancouver	Divine R, Dang HV, Ueda G, Fallas JA, Vulovic I, Sheffler W, et al.. Designed Proteins Assemble Antibodies Into Modular Nanocages. Science. 2021;372(6537):-.
BibTex	@article{ author = {Divine R and Dang HV and Ueda G and Fallas JA and Vulovic I and Sheffler W and Saini S and Zhao YT and Raj IX and Morawski PA and Jennewein MF and Homad LJ and Wan YH and Tooley MR and Seeger F and Etemadi A and Fahning ML and Lazarovits J and Roederer A and Walls AC and Stewart L and Mazloomi M and King NP and Campbell DJ and Mcguire AT and Stamatatos L and Ruoholabaker H and Mathieu J and Veesler D and Baker D}, title = {Designed Proteins Assemble Antibodies Into Modular Nanocages}, journal = {Science}, volume = {372}, number = {6537}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Divine R AU - Dang HV AU - Ueda G AU - Fallas JA AU - Vulovic I AU - Sheffler W AU - Saini S AU - Zhao YT AU - Raj IX AU - Morawski PA AU - Jennewein MF AU - Homad LJ AU - Wan YH AU - Tooley MR AU - Seeger F AU - Etemadi A AU - Fahning ML AU - Lazarovits J AU - Roederer A AU - Walls AC AU - Stewart L AU - Mazloomi M AU - King NP AU - Campbell DJ AU - Mcguire AT AU - Stamatatos L AU - Ruoholabaker H AU - Mathieu J AU - Veesler D AU - Baker D TI - Designed Proteins Assemble Antibodies Into Modular Nanocages JO - Science VL - 372 IS - 6537 SP - EP - PY - 2021 ER -

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Abstract