Virus-like particles (VLPs) are a class of virus-like nanoscale particles with structures similar to real viruses but lacking viral genes, thus possessing high biosafety [1]. In recent years, the VLP technology platform has attracted widespread attention in the field of biotechnology, particularly making significant progress in vaccine development, drug delivery, gene therapy, and immunomodulation [2].
VLPs are particles formed by the assembly of viral structural proteins, with sizes and shapes similar to natural viruses [3]. According to their origin and structural characteristics, VLPs can be divided into various types, including RNA viruses, DNA viruses, and chimeric viruses [4]. VLPs possess the immunogenicity of natural viruses but lack infectivity and replicative capabilities, making them safe and effective vaccine carriers [5].
The VLP technology platform can be produced through various host cell systems, such as insect cells, mammalian cells, and plant cells [6]. Among these, insect cell systems are the most commonly used production method, offering advantages such as high production efficiency and ease of scaling up [7]. Additionally, plant cell systems provide benefits such as environmentally friendly, low-cost production, and rapid response to epidemics [8].
Mammalian cell expression systems are another essential choice for the VLP technology platform production. Compared to insect and plant cell systems, mammalian cell expression systems are closer to the physiological environment of human cells, offering higher fidelity in protein translation, modification, and folding. This allows VLPs expressed in mammalian cells to exhibit immunogenicity and bioactivity closer to natural viruses [9].
Common mammalian cell expression systems include CHO (Chinese Hamster Ovary) cells, HEK293 (Human Embryonic Kidney 293) cells, and BHK (Baby Hamster Kidney) cells. Among these, CHO cells are the most commonly used mammalian cell expression system for industrial production, offering high production efficiency and scalability. However, compared to insect and plant cell systems, mammalian cell production has higher costs and may pose risks of pathogen contamination during the production process [10].
Based on the mammalian cell expression system, the VLP technology platform developed by CUSABIO has improved the production process, significantly enhancing expression levels and reducing cell toxicity.
VLPs offer several advantages in expressing recombinant proteins, mainly manifested in the following aspects:
High simulation of natural virus structure: The size, shape, and spatial conformation of viral surface proteins in VLPs are highly similar to natural viruses [11]. This allows VLPs to highly simulate the behavior of natural viruses within organisms, effectively inducing immune responses.
Safety: Since VLPs do not contain viral genes, they lack infectivity and replicative capabilities, providing high biosafety [12]. This makes VLPs ideal candidates for vaccine research and drug delivery applications.
High immunogenicity: The multivalence and high simulation of natural virus surface proteins endow VLPs with high immunogenicity. In vaccine research, VLPs can effectively activate B cell and T cell immune responses, thereby providing robust immune protection [13].
Plasticity: By employing genetic engineering techniques, exogenous antigens can be fused into the structural proteins of VLPs, generating chimeric VLPs. This design allows exogenous antigens to be presented in the form of VLPs within the body, thereby enhancing immunogenicity [14].
Diversity: VLPs can be produced through various host cell systems, including bacteria, yeast, insect cells, mammalian cells, and plant cells. This provides a wide range of choices for implementing VLPs in different fields [15].
As can be seen, VLPs possess numerous advantages in expressing recombinant proteins, giving them extensive application potential in vaccine research, drug delivery, and immunomodulation.
VLPs exhibit significant advantages in expressing transmembrane proteins, mainly manifested in the following aspects:
Maintenance of spatial conformation: Transmembrane proteins have complex three-dimensional structures, and their functions often rely on the correct spatial conformation on the cell membrane. Compared to other expression systems, VLPs better simulate the membrane environment of natural viruses, helping maintain the correct spatial conformation and bioactivity of transmembrane proteins [16].
Protein translation and modification: VLPs can be produced through mammalian cell expression systems, which offer higher fidelity in protein translation, folding, and modification, contributing to the correct expression and functionality of transmembrane proteins [17].
Enhanced immunogenicity: VLPs can serve as immunogenic delivery carriers, presenting transmembrane proteins to the immune system in the form of natural viruses. This approach can enhance the immunogenicity of transmembrane proteins, eliciting a more robust immune response [18].
Functional screening: Using VLPs to express transmembrane proteins allows for convenient functional screening, such as measuring transmembrane protein affinity or optimizing antibody affinity. This helps study the biological functions of transmembrane proteins and develop related drugs [19].
The advantages of VLPs in expressing transmembrane proteins help address key issues in transmembrane protein research, such as protein expression, functional screening, and immunogenicity.
CUSABIO has specifically developed an enveloped VLP technology platform based on the HEK293 expression system. The prepared enveloped VLPs display correctly folded, multiple-pass transmembrane proteins on their inherent vesicle membranes, exhibiting complete bioactivity.
Platform advantages:
Case Study:
● Recombinant Human Somatostatin receptor type 2(SSTR2)-VLPs (Active)
● Recombinant Human Claudin-6(CLDN6)-VLPs (Active)
References
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[14] Lua, L. H. L., Connors, N. K., Sainsbury, F., Chuan, Y. P., Wibowo, N., & Middelberg, A. P. J. (2014). Bioengineering virus-like particles as vaccines. Biotechnology and Bioengineering, 111(3), 425-440.
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