Designed proteins assemble antibodies into modular nanocages

Author:

Divine Robby12ORCID,Dang Ha V.1ORCID,Ueda George12ORCID,Fallas Jorge A.12ORCID,Vulovic Ivan12ORCID,Sheffler William2ORCID,Saini Shally13ORCID,Zhao Yan Ting134,Raj Infencia Xavier13ORCID,Morawski Peter A.5ORCID,Jennewein Madeleine F.6ORCID,Homad Leah J.6ORCID,Wan Yu-Hsin6ORCID,Tooley Marti R.2,Seeger Franziska12,Etemadi Ali27,Fahning Mitchell L.5ORCID,Lazarovits James12ORCID,Roederer Alex2ORCID,Walls Alexandra C.1ORCID,Stewart Lance2ORCID,Mazloomi Mohammadali7ORCID,King Neil P.12ORCID,Campbell Daniel J.5ORCID,McGuire Andrew T.68ORCID,Stamatatos Leonidas68ORCID,Ruohola-Baker Hannele13ORCID,Mathieu Julie39ORCID,Veesler David1ORCID,Baker David1210ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

2. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

3. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.

4. Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA 98195, USA.

5. Benaroya Research Institute, Seattle, WA 98101, USA.

6. Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.

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, WA 98195, USA.

9. Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.

10. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

Abstract

Integrating form and function for design Antibodies are broadly used in therapies and as research tools because they can be generated against a wide range of targets. Efficacy can often be increased by clustering antibodies in multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein and the other is the antibody itself. Computationally designed proteins drive the assembly of antibody nanocages in a range of architectures, allowing control of the symmetry and the antibody valency. The multivalent display enhances antibody-dependent signaling, and nanocages displaying antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein effectively neutralize pseudovirus. Science , this issue p. eabd9994

Funder

National Science Foundation

National Institutes of Health

National Center for Advancing Translational Sciences

Wellcome

Howard Hughes Medical Institute

Washington Research Foundation

National Institute of Allergy and Infectious Diseases

National Institute of General Medical Sciences

U.S. Department of Defense

American Heart Association

Wu Tsai Translational Investigator Fund

Washington State General Operating Fund for the Institute for Protein Design

Nan Fung Life Sciences Translational Investigator Fund

Audacious Project at the Institute for Protein Design

Nordstrom-Barrier Directors Fund at the Institute for Protein Design

Pew Biomedical Scholars Award

NIAID/NIH

Fast Grants

Fred Hutch COVID-19 Research Fund

NIH/NCI Cancer Center

Burroughs Wellcome Investigators in the Pathogenesis of Infectious Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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