Cytosolic RNA de-pletion by polymeric nanoparticles

A challenge for miRNA therapeutics is to maintain the stability and consistency of miRNAs in circulation. Naked miRNAs are degraded by nucleases within seconds or are rapidly removed by renal excretion. Thus, suitable delivery systems are needed that stabilise the antisense DNA, allow efficient uptake by the cells, while avoiding off-targets. They should also be adjustable so they can deplete any target RNA.

The invention describes nanoparticles (NP) composed of biopolymer-DNA conjugates that have the ability to bind and inactivate cytosolic miRNA in cells. Two types of NPs are described: (1) 'sponge' NPs, which bind miRNA in a condensed state, as the binding sites are exposed and (2) transient NPs, which open in the cell after initial contact with the miRNA and can bind further miRNAs. The transient NP can act as a targeted drug delivery system, releasing a drug only upon contact with a specific trigger DNA sequence. The design of the DNA sequences that stabilise the NPs can be freely adapted to any cytosolic RNA target. It was shown that these NPs were successfully taken up, were able to escape from endo-somes and were effective in silencing miRNA.