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Computational design of non-porous, pH-responsive antibody nanoparticles
- Source :
- bioRxiv
- Publication Year :
- 2023
- Publisher :
- Cold Spring Harbor Laboratory, 2023.
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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: ade novodesigned 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.
- Subjects :
- Article
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- bioRxiv
- Accession number :
- edsair.doi.dedup.....08485ba26a36e4b67dd39fd83b59e0cd