A pH-Responsive Virus-Like Particle as a Protein Cage for a Targeted Delivery
Kwan-Jip Kim1, Gijeong Kim1, Jin-Ho Bae1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejon, 34141, South Korea.
Advanced Healthcare Materials
|November 15, 2023
Summary
Researchers engineered a pH-responsive virus-like particle (VLP) using bacteriophage P22 coat protein. This self-assembling protein structure can be triggered to disassemble at acidic pH for targeted delivery applications.
Area of Science:
- Biotechnology
- Nanotechnology
- Structural Biology
Background:
- Stimuli-responsive protein self-assembly is crucial for developing advanced protein nanocages.
- Virus-like particles (VLPs) offer versatile platforms for biotechnological and medical applications.
Purpose of the Study:
- To design and develop a pH-responsive VLP capable of controlled assembly and disassembly.
- To enable targeted delivery of therapeutic cargo into cells based on pH changes.
Main Methods:
- Computational design of bacteriophage P22 coat protein subunits with histidine substitutions.
- Iterative evaluation of subunit interactions at neutral and acidic pH.
- Cryo-electron microscopy (cryo-EM) to determine VLP structure and pH-triggered disassembly mechanism.
Main Results:
- Successfully designed a VLP exhibiting significant pH-dependent structural transitions.
- Identified the structural basis for pH-triggered disassembly.
- Demonstrated targeted delivery of cytotoxic protein cargo into tumor cells.
Conclusions:
- Developed a novel self-assembling protein architecture with tunable pH responsiveness.
- The designed VLP platform shows potential for targeted drug delivery and other biomedical applications.
- Provides a strategy for engineering functional protein assemblies for diverse applications.
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