Pseudouridine-modified RNA probe for label-free electrochemical detection of nucleic acids on 2D MoS2 nanosheets.

RNA modification, particularly pseudouridine (Ψ), has played an important role in the development of the mRNA-based COVID-19 vaccine. This is because Ψ enhances RNA stability against nuclease activity and decreases the anti-RNA immune response. Ψ also provides structural flexibility to RNA by enhancing base stacking compared with canonical nucleobases. In this report, we demonstrate the first application of pseudouridine-modified RNA as a probe (Ψ-RNA) for label-free nucleic acid biosensing. It is known that MoS2 has a differential affinity for nucleic acids, which may be translated into a unique electronic signal. Herein, the Ψ-RNA probe interacts with the pristine MoS2 surface and causes a change in interfacial electrochemical charge transfer in the MoS2 nanosheets. Compared with an unmodified RNA probe, Ψ-RNA exhibited faster adsorption and higher affinity for MoS2. Moreover, Ψ-RNA could bind to complementary RNA and DNA targets with almost equal affinity when engaged with the MoS2 surface. Ψ-RNA maintained robust interactions with the MoS2 surface following the hybridization event, perhaps through its extra amino group. The detection sensitivity of the Ψ-RNA/MoS2 platform was as low as 500 attomoles, while the results also indicate that the probe can distinguish between complementary targets, single mismatches, and non-complementary nucleic acid sequences with statistical significance. This proof-of-concept study shows that the Ψ-RNA probe may solve numerous problems of adsorption-based biosensing platforms due to its stability and structural flexibility.

DNA interfaces with dimensional materials for biomedical applications.

DNA interfaces with nano, micro, and macro materials have gained widespread attention for various applications. Such interfaces exhibit distinct functions and properties not only due to the unique properties of interfacing materials but also sequence- and conformation-dependent characteristics of the DNA. Therefore, DNA interfaces with diverse dimensional materials have advanced our understanding of the interaction mechanisms and the properties of such interfaces. The unique interfacial properties of such novel materials have applications in nanotechnology, biophysics, cell biology, biosensing, and bioelectronics. The field is growing rapidly with the frequent emergence of new interfaces carrying remarkable interfacial character. In this review article, we have classified the DNA interfaces into 0D, 1D, 2D, and 3D categories based on the types of dimensional materials. We review the key efforts made in the last five years and focus on types of interfaces, interfacing mechanisms, and their state-of-the-art applications. This review will draw a general interest because of the diversity in the DNA materials science but also the unique applications that will play a cutting-edge role in biomedical and biosensing research.