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Review
. 2024;19(12):1103-1115.
doi: 10.2217/nnm-2023-0362. Epub 2024 Apr 17.

Virus-like particles derived from bacteriophage MS2 as antigen scaffolds and RNA protective shells

Antonina Naskalska  1 , Jonathan Gardiner Heddle  1   2
Affiliations
Review

Virus-like particles derived from bacteriophage MS2 as antigen scaffolds and RNA protective shells

Antonina Naskalska et al. Nanomedicine (Lond). 2024.

Abstract

The versatile potential of bacteriophage MS2-derived virus-like particles (VLPs) in medical biotechnology has been extensively studied during the last 30 years. Since the first reports showing that MS2 VLPs can be produced at high yield and relatively easily engineered, numerous applications have been proposed. Particular effort has been spent in developing MS2 VLPs as protective capsules and delivery platforms for diverse molecules, such as chemical compounds, proteins and nucleic acids. Among these, two are particularly noteworthy: as scaffolds displaying heterologous epitopes for vaccine development and as capsids for encapsulation of foreign RNA. In this review, we summarize the progress in developing MS2 VLPs for these two areas.

Keywords: RNA delivery; RT-PCR; bionano; capsid; drug delivery; phage; protein cage; protein engineering; vaccines.

Plain language summary

Hollow, nanosized protein particles have many potential uses. If they can be appropriately engineered, they may for example be able to carry therapeutic cargoes to diseased cells or be used as a vaccine where appropriate antigens are mounted on their external surface. Many viruses offer a ready-made protein particle, the capsid, which can be made hollow by exclusion of the viral genetic material. MS2 is a virus that targets bacteria – a bacteriophage – which is well characterized and has been developed over many years for a number of applications. It has particular promise for development as a vaccine and for RNA delivery, both of which are reviewed here.

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Conflict of interest statement

The authors declare the following competing financial interest: JG Heddle is the founder of and holds equity in nCage Therapeutics LLC, which aims to commercialize protein cages for therapeutic applications. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Structure of MS2 bacteriophage. (A) Crystal structure of MS2 (PDB 2MS2) [5]. CPs A, B and C are colored lime green, dark pink and coral blue, respectively. (B) Schematic representation of the structure of MS2 showing that CP forms dimers adopting two conformations: called A/B and C/C as indicated, adapted from Biela et al. published under a CC BY 4.0 license (http://creativecommons.org/licenses/by/4.0/) [6]. (C & D) Close-up orthogonal views of the structures of two dimer types represented as ribbons and colored as in panel (A). CP: Coat protein; PDB: Protein Data Bank.
Figure 2.
Figure 2.
Comparison of expression systems used to encapsulate foreign RNA in MS2 virus-like particles. In the single-plasmid system (top) the maturase, coat protein and RNA sequence to be packaged are encoded on one transcript. Alternatively, maturase and coat protein are encoded on one transcript and the RNA sequence on another, both in the same plasmid. In the two-plasmid system (bottom) the maturase, coat protein and RNA sequence to be packaged are encoded on two separate transcripts, from two different plasmids. Figure created with Biorender.com. VLP: Virus-like particle.
Figure 3.
Figure 3.
Reported developments in the field of RNA packaging into MS2 virus-like particles. Figure created with Biorender.com. VLP: Virus-like particle.
See this image and copyright information in PMC

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