A PH-Responsive Virus-Like Particle As a Protein Cage for a Targeted Delivery

Overview

Journal Adv Healthc Mater

Specialties Biomedical Engineering
Biotechnology

Date 2023 Nov 15

PMID 37966427

Authors

Kwan-Jip Kim

Gijeong Kim

Jin-Ho Bae

Ji-Joon Song

Hak-Sung Kim

Affiliations

Soon will be listed here.

Abstract

A stimuli-responsive protein self-assembly offers promising utility as a protein nanocage for biotechnological and medical applications. Herein, the development of a virus-like particle (VLP) that undergoes a transition between assembly and disassembly under a neutral and acidic pH, respectively, for a targeted delivery is reported. The structure of the bacteriophage P22 coat protein is used for the computational design of coat subunits that self-assemble into a pH-responsive VLP. Subunit designs are generated through iterative computational cycles of histidine substitutions and evaluation of the interaction energies among the subunits under an acidic and neutral pH. The top subunit designs are tested and one that is assembled into a VLP showing the highest pH-dependent structural transition is selected. The cryo-EM structure of the VLP is determined, and the structural basis of a pH-triggered disassembly is delineated. The utility of the designed VLP is exemplified through the targeted delivery of a cytotoxic protein cargo into tumor cells in a pH-dependent manner. These results provide strategies for the development of self-assembling protein architectures with new functionality for diverse applications.

Citing Articles

Virus-like Particles as Vaccines for Allergen-Specific Therapy: An Overview of Current Developments.

Berreiros-Hortala H, Vilchez-Pinto G, Diaz-Perales A, Garrido-Arandia M, Tome-Amat J Int J Mol Sci. 2024; 25(13).

PMID: 39000536 PMC: 11242184. DOI: 10.3390/ijms25137429.

A pH-Responsive Virus-Like Particle as a Protein Cage for a Targeted Delivery.

Kim K, Kim G, Bae J, Song J, Kim H Adv Healthc Mater. 2023; 13(4):e2302656.

PMID: 37966427 PMC: 11469083. DOI: 10.1002/adhm.202302656.

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