Virus-like Nanoparticle Production
The research and development of viruslike nanoparticles (VLNPs) exploits the structural characteristics of virus capsids as bionanotechnology platforms with great potential in drug delivery and molecular imaging. Creative Biostructure now provides Viruslike Nanoparticles as an emerging tool for targeted cancer diagnostics and therapeutics. The particles could eventually lead to safe, targeted therapies that fight infections and avoid antibiotic resistance.
The term ‘VLNPs’ refers to the noninfectious protein shells, or capsids, comprised of virus-derived structural proteins, modified to be of use in nanotechnology. Some VLNPs derived from productive infections can be disassembled and reassembled in vitro, allowing isolation from the infectious nucleic acid component. Abundant researches have been performed thus far and outline the potential for these VLNPs to become highly effective delivery vehicles that overcome the many challenges encountered for targeted delivery of therapeutic cargo.
Figure 1. Escherichia coli cells (left) incubated with rod-shaped nanoparticles (middle) are damaged less than those exposed to spherical nanoparticles (right).
Table 1. Commonly used VLNPs and their production information
| VLNP | Virus type | VLNP outer diameter (nm) | VLNP inner diameter (nm) | VLNP geometry | VLNP subunits |
| HBVc | Animal virus | 35 | 26 | T=4 icosahedral | 240 coat proteins (120 dimers) |
| MS2 | Bacteriophoage | 27 | 15 | T=3 icosahedral | 180 coat proteins (90 dimers) |
| Qβ | Bacteriophoage | 28 | 21 | T=3 icosahedral | 180 coat proteins (90 dimers) |
| P22 | Bacteriophoage | 58-64 | 48-50 | T=7 icosahedral | 180 coat proteins + 100-300 removable scaffold proteins |
| CCMV | Plant virus | 28 | 18 | T=3 icosahedral | 180 coat proteins (90 dimers) |
| CPMV | Plant virus | 28-31 | 22 | T=3 icosahedral | 60 large + 60 small coat proteins |
Structural biology has long been associated with the biomolecular engineering of virus capsids and is a fundamental aspect of physical virology and the development VLNP-based technologies. A key advantage of VLNPs as nanoparticles is the availability of structural models with near-atomic detail; they enable the rational modification of capsid proteins with molecular precision by standard protein engineering techniques and bioconjugation chemistries, or a combination of these via the introduction of unnatural amino acid residues. The deceptively simple architecture of virus capsids results in a powerful platform to re-engineer form and function, for example, tropism and cellular uptake pathway, or programmable cargo loading.
Advantages of VLNPs are that they:
- Can be produced using cell-free protein synthesis
- Can load small molecules, nucleic acids, and proteins
- Can be stabilized with disulfide bonds
- Can incorporate non-natural amino acids for ease of surface functionalization through the “click” reaction
- Can be functionalized to display antibody fragments for specific cellular targeting
- Can be functionalized to display PEG to avoid the immune system (not shown for HBVc VLNPs)
- Will disassemble in the reducing conditions of the cytosol to release their cargo (not shown for MS2 VLNPs)
Together with our Membrane Protein production and VLP construction services, Creative Biostructure now provides modern and excellent Virus-Like Nanoparticles strategies for the therapeutic targets of your interest.
Please feel free to contact us for a detailed quote.
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References
- Prachi Patel, (2016) Viruslike nanoparticles kill drug- resistant bacteria. Chemical & Engineering News. August 24, 2017.
- Marcus J. Rohovie, (2016) Virus-like particles: Next-generation nanoparticles for targeted therapeutic delivery. Bioengineering & Translational Medicine 2017; 2: 43–57.
- Frank Sainsbury, (2017) Virus-like nanoparticles: emerging tools for targeted cancer diagnostics and therapeutics. Therapeutic Delivery. VOL. 8, NO. 12.
