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Affinity chromatography for virus-like particle manufacturing: Challenges, solutions, and perspectives
Jing Ma1, Zengquan Tian1, Qinghong Shi1
1Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
Virus-like particle (VLP) production faces downstream processing challenges. This review analyzes affinity chromatography for VLP purification, highlighting the need for universal ligands and process intensification for efficient manufacturing.
Area of Science:
- Biotechnology and bioprocessing
- Protein purification
- Vaccine development
Background:
- Virus-like particles (VLPs) are increasingly used in vaccines and viral vectors, driving demand for commercial production.
- Current VLP manufacturing efficiency, particularly in downstream processing, lags behind recombinant protein therapeutics.
- Affinity chromatography is a key purification technique for VLPs, but faces challenges due to VLP diversity and process complexity.
Purpose of the Study:
- To comprehensively analyze the challenges of affinity chromatography in VLP purification.
- To review engineered affinity ligands, discovery methods, and process influences for VLP purification.
- To provide guidance for developing efficient VLP manufacturing processes.
Main Methods:
- Review of engineered affinity ligands and matrices for VLP purification.
- Discussion of phage display and computer-assisted design for high-affinity peptide ligand discovery.
- Analysis of VLP purification by affinity chromatography, considering virus characteristics and chromatographic modes.
Main Results:
- Existing affinity ligands struggle to balance universality, selectivity, and mild operating conditions.
- Phage display and computational methods offer efficient ligand discovery.
- VLP purification is significantly influenced by virus size, variation, ligand type, and chromatographic mode.
Conclusions:
- Technical innovations, process intensification, and standardization are crucial for efficient VLP manufacturing.
- Discovery of universal ligands, use of gigaporous matrices, and platform technologies are emphasized.
- This review offers insights into affinity chromatography for VLP purification and future manufacturing development.
