Virus-like nanoparticles encapsulating functional riboswitches lock-in toxic metabolites.
The researchers exploit the self-assembly of MS2 bacteriophage coat protein dimers into an icosahedral virus-like particle (VLP) driven by an RNA stem-loop structure for riboswitch encapsulation. In particular, they designed a double expression plasmid that codes for the MS2 coat protein dimer comprising of a riboswitch RNA sequence at the 5′ end. When transfected into E. coli cells, this plasmid produces homogenous VLPs of ~30 nm in diameter, encapsulating the riboswitch. This renders the encapsulated riboswitch resistant to nucleases and confers long-term storage stability for up to nine months at 4 °C. “Our lab has the know-how on production of self-assembled, nucleic acid encapsulated VLPs. On top of that, the extensive groundwork on MS2-capsid-based VLPs as engineered nanocarriers was already laid4; thus, MS2 was the obvious choice”, explains Ehud Gazit, the corresponding author of the study.
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