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Computational design of non-porous, pH-responsive antibody nanoparticles.
Yang, Erin C; Divine, Robby; Miranda, Marcos C; Borst, Andrew J; Sheffler, Will; Zhang, Jason Z; Decarreau, Justin; Saragovi, Amijai; Abedi, Mohamad; Goldbach, Nicolas; Ahlrichs, Maggie; Dobbins, Craig; Hand, Alexis; Cheng, Suna; Lamb, Mila; Levine, Paul M; Chan, Sidney; Skotheim, Rebecca; Fallas, Jorge; Ueda, George; Lubner, Joshua; Somiya, Masaharu; Khmelinskaia, Alena; King, Neil P; Baker, David.
Afiliación
  • Yang EC; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Divine R; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Miranda MC; Graduate Program in Biological Physics, Structure & Design, University of Washington, Seattle, WA, USA.
  • Borst AJ; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Sheffler W; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Zhang JZ; Graduate Program in Biochemistry, University of Washington, Seattle, WA, USA.
  • Decarreau J; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Saragovi A; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Abedi M; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Goldbach N; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Ahlrichs M; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Dobbins C; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Hand A; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Cheng S; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lamb M; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Levine PM; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Chan S; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Skotheim R; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Fallas J; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Ueda G; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lubner J; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Somiya M; Technical University of Munich, Munich, Germany.
  • Khmelinskaia A; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • King NP; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Baker D; Institute for Protein Design, University of Washington, Seattle, WA, USA.
bioRxiv ; 2023 Apr 18.
Article en En | MEDLINE | ID: mdl-37131615
ABSTRACT
Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and important for targeted delivery of biologics. We describe the design of octahedral non-porous nanoparticles with the three symmetry axes (four-fold, three-fold, and two-fold) occupied by three distinct protein homooligomers a de novo designed tetramer, an antibody of interest, and a designed trimer programmed to disassemble below a tunable pH transition point. The nanoparticles assemble cooperatively from independently purified components, and a cryo-EM density map reveals that the structure is very close to the computational design model. The designed nanoparticles can package a variety of molecular payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between to 5.9-6.7. To our knowledge, these are the first designed nanoparticles with more than two structural components and with finely tunable environmental sensitivity, and they provide new routes to antibody-directed targeted delivery.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos