Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery.

Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin heavy chain and light chain for a targeted protein delivery, is presented. The clathrin heavy and light chains are redesigned and associated with each other, and the resulting triskelion unit further self-assembled into a clathrin assembly with the size of about 28 nm in diameter. The clathrin assembly is dual-functionalized with a protein cargo and a targeting moiety using two different orthogonal protein-ligand pairs through one-pot reaction. The functionalized clathrin assembly exhibits about a 900-fold decreased KD value for a cell-surface target due to avidity compared to a native targeting moiety. The utility of the clathrin assembly is demonstrated by an efficient delivery of a protein cargo into tumor cells in a target-specific manner, resulting in a strong cytotoxic effect. The present approach can be used in the creation of protein assemblies with multimodality. © 2022 Wiley-VCH GmbH.

Citation

Hong-Sik Kim, Jin-Ho Bae, Gijeong Kim, Ji-Joon Song, Hak-Sung Kim. Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery. Small (Weinheim an der Bergstrasse, Germany). 2023 Feb;19(8):e2204620

Mesh Tags

Substances

PMID: 36456203

search → result