Computational design of non-porous, pH-responsive antibody nanoparticles
Computational design of non-porous, pH-responsive antibody nanoparticles
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.
Decarreau Justin、Divine Robby、Borst Andrew J.、Saragovi Amijai、Abedi Mohamad、Ahlrichs Maggie、Hand Alexis、Levine Paul M.、Somiya Masaharu、King Neil P.、Cheng Suna、Dobbins Craig、Yang Erin C.、Khmelinskaia Alena、Lamb Mila、Miranda Marcos C.、Sheffler Will、Ueda George、Fallas Jorge、Skotheim Rebecca、Chan Sidney、Goldbach Nicolas、Lubner Joshua、Zhang Jason Z、Baker David
Institute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of Washington||Graduate Program in Biochemistry, University of Washington||Department of Chemistry, University of CaliforniaInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||SANKEN, Osaka UniversityInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of Washington||Graduate Program in Biological Physics, Structure & Design, University of WashingtonInstitute for Protein Design, University of Washington||Transdisciplinary Research Area ?°Building Blocks of Matter and Fundamental Interactions (TRA Matter)?±, University of Bonn||Life and Medical Sciences Institute, University of BonnInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University HospitalInstitute for Protein Design, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Technical University of MunichInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of WashingtonInstitute for Protein Design, University of Washington||Department of Biochemistry, University of Washington||Howard Hughes Medical Institute, University of Washington
生物科学研究方法、生物科学研究技术生物工程学分子生物学
Decarreau Justin,Divine Robby,Borst Andrew J.,Saragovi Amijai,Abedi Mohamad,Ahlrichs Maggie,Hand Alexis,Levine Paul M.,Somiya Masaharu,King Neil P.,Cheng Suna,Dobbins Craig,Yang Erin C.,Khmelinskaia Alena,Lamb Mila,Miranda Marcos C.,Sheffler Will,Ueda George,Fallas Jorge,Skotheim Rebecca,Chan Sidney,Goldbach Nicolas,Lubner Joshua,Zhang Jason Z,Baker David.Computational design of non-porous, pH-responsive antibody nanoparticles[EB/OL].(2025-03-28)[2025-05-18].https://www.biorxiv.org/content/10.1101/2023.04.17.537263.点此复制
评论