An ultrasensitive guanine wire-based resonance light scattering method using G-quadruplex self-assembly for...

An enzyme-free resonance light scattering (RLS) method is described for the determination of microRNA-122. A guanine nanowire (G-wire) is used that consists of a predesigned DNA1 and a G-quadruplex sequence DNA2. These hybridize with microRNA-122 and partially hybridize with DNA2. After formation of stable double strands with DNA1, DNA2 is released. On addition of K⁺ and Mg²⁺ ions, the G-quadruplex sequences undergo self-assembly to form long filamentous G-wires. This increases the intensity of RLS. A 6.1 pM detection limit was obtained, and the linear response covers the 50 pM to 300 nM microRNA concentration range. The method was successfully applied to the quantitation of microRNA-122 in hepatocellular carcinoma cell lysates. Conceivably, this assay can be extended to other RLS methods for biomarker detection by simply changing the sequence of DNA1. Graphical abstract The G-quadruplex sequences of DNA2 were locked with DNA1. The G-quadruplex fragments of DNA2 were released after the hybridization of microRNA-122 with DNA1. These liberated G-quadruplex sequences were self-assembled into long filamentous guanine nanowires (G-wires) which increased resonance light intensity in the presence of Mg²⁺.