Synthetic Virions (SVs), which undergo a pH-dependent assembly and dis-assembly to effect the capture and subsequent release of a therapeutic payload have been developed.
The SVs enter cells rapidly via receptor-mediated endocytosis taking advantage of their multidentate target ligands, and many cargoes including mRNAs, siRNA, antisense DNAs, toxins and enzymes have been shown to escape the late endosomal compartment and enter the cytoplasm. Cell targeting can be enhanced through ligand attachment to the virion.
Once internalised the lowering pH of the pathway leads to reversal of the particle assembly and release of any drug conjugates.
SV assembly is routine, the protein starting materials can be produced in simple bacterial fermentation, and the process can be easily automated on the 100 mg – 1 g scale. MS2 capsids are immunogenic but non-toxic in animals.