Sensing Picomolar Concentrations of RNA Using Switchable Plasmonic Chirality

Detecting small sequences of RNA in biological samples such as microRNA or viral RNA demands highly sensitive and specific methods. Here, a reconfigurable DNA origami template has been used where a chiral arrangement of gold nanorods on the structure can lead to the generation of strong circular dichroism (CD). Switching of the cross-like DNA structure is achieved by the addition of nucleic acid sequences that arrest the structure in one of the possible chiral states by specific molecular recognition. A specific sequence can thus be detected via the resulting changes of the plasmonic CD spectrum. We show the sensitive and selective detection of a target RNA sequence from the hepatitis C virus genome. In our design, the RNA binds to a complementary sequence that is part of the lock mechanism and thus leads to the formation of a defined state of the plasmonic system with a distinct optical response. With this approach, we were able to detect this specific RNA sequence at concentrations as low as 100 pM. We further show the stability of our system in human serum and thus pave the way towards the development of fast optical-based detectors for pathogenic RNA.