A novel delivery platform based on Bacteriophage MS2 virus-like particles

Abstract

Our objective here is to review the novel delivery platform based on Bacteriophage MS2 virus-like particles (VLPs), including introduction to their structure, their potential as a delivery platform, and their expected use in medicine and other fields. Bacteriophage MS2 VLPs are nanoparticles devoid of viral genetic material and can self-assemble from the coat protein into an icosahedral capsid. As a novel delivery platform, they possess numerous features that make them suitable and attractive for targeted delivery of RNAs or DNAs, epitope peptides, and drugs within the protein capsid. In short, as a novel delivery platform, MS2 VLPs are suitable for delivery of targeted agents and hold promise for use in diagnostics, vaccines, and therapeutic modalities.

Keywords: Bacteriophage MS2; Delivery platform; In vitro diagnostic; Therapy; Vaccine; Virus-like particles.

Fig. 1

Structure of Bacteriophage MS2. (A) External morphological characteristics of Bacteriophage MS2 with the triangulation number T = 3. The left panel depicts a geometric model of MS2. The middle panel depicts surface representation of Bacteriophage MS2: a crystal structure of in vitro assembled MS2 coat protein (CP) with synthetic RNA hairpins. A/B dimers are blue and green. C/C dimers are purple. The right panel depicts an electron-microscopy image of wild-type MS2. The scale bar is 100 nm. (B) Structures of the A/B and C/C dimers. The FG loop (highlighted) exists in an extended conformation in the A and C subunits but is bent back toward the core of the protein in B subunits. Sixty A/B dimers and 30C/C dimers assemble into the icosahedron of MS2. (C) Genetic map of the MS2 genome. The genome of Bacteriophage MS2encodes four proteins: CP (the major protein), the maturation protein (A-protein), the replicase (an RNA polymerase necessary for genome multiplication), and the lysis protein. Adapted from Bleckley and Schroeder (2012), Borodavka et al. (2012), Li et al. (2014), and Pan et al., 2012a, Pan et al., 2012b. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Roles of MS2 virus-like particles (VLPs). (A) Delivery of mRNAs. After being packaged into MS2 VLPs, an mRNA-based vaccine can easily stimulate the immune system and serve as an effective vaccine. (B) Delivery of peptides. Exogenous peptides can be easily recombined with MS2VLPs via genetic engineering, and the chimeric VLPs are strongly immunogenic when carrying either B- or T-cell epitopes. (C) Delivery of miRNAs. miRNAs perform powerful gene-regulatory functions in many diseases. As a novel attractive delivery system, MS2 VLPs bonded with miRNAs can be applied to gene therapy. (D) Delivery of drugs. MS2VLPs possess several features that make them attractive as potential nanocarriers for passive and targeted drug delivery and can be effective against certain diseases (in animal models). Adapted from Pan et al., 2012a, Pan et al., 2012b. (E) MS2 VLP-based RNAs and DNAs (armored RNA or DNA). Owing to a structure similar to that of the native RNA virus and good biosafety, recombinant MS2 VLPs are widely used as “control”, “standard”, and “calibrator” in assays for viruses.