Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery (Small 8/2023) |
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Authors: | Hong-Sik Kim Jin-Ho Bae Gijeong Kim Ji-Joon Song Hak-Sung Kim |
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Affiliation: | Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea |
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Abstract: | 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. |
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Keywords: | avidity clathrin functionalization protein assembly protein delivery |
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