학술논문
Computational design of non-porous pH-responsive antibody nanoparticles
Document Type
Article
Author
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
Source
Nature Structural and Molecular Biology; 20240101, Issue: Preprints p1-9, 9p
Subject
Language
ISSN
15459993; 15459985
Abstract
Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and is important for targeted delivery of biologics. Here we describe the design of octahedral non-porous nanoparticles with a targeting antibody on the two-fold symmetry axis, a designed trimer programmed to disassemble below a tunable pH transition point on the three-fold axis, and a designed tetramer on the four-fold symmetry axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components, and a cryo-EM density map closely matches the computational design model. The designed nanoparticles can package protein and nucleic acid payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between 5.9 and 6.7. The ability to incorporate almost any antibody into a non-porous pH-dependent nanoparticle opens up new routes to antibody-directed targeted delivery.