Turn-on RNA Mango Beacons for trans-acting fluorogenic nucleic acid detection.

The Mango I and II RNA aptamers have been widely used in vivo and in vitro as genetically encodable fluorogenic markers that undergo large increases in fluorescence upon binding to their ligand, TO1-Biotin. However, while studying nucleic acid sequences, it is often desirable to have trans-acting probes that induce fluorescence upon binding to a target sequence. Here, we rationally design three types of light-up RNA Mango Beacons based on a minimized Mango core that induces fluorescence upon binding to a target RNA strand. Our first design is bimolecular in nature and uses a DNA inhibition strand to prevent folding of the Mango aptamer core until binding to a target RNA. Our second design is unimolecular in nature, and features hybridization arms flanking the core that inhibit G-quadruplex folding until refolding is triggered by binding to a target RNA strand. Our third design builds upon this structure, and incorporates a self-inhibiting domain into one of the flanking arms that deliberately binds to, and precludes folding of, the aptamer core until a target is bound. This design separates G-quadruplex folding inhibition and RNA target hybridization into separate modules, enabling a more universal unimolecular beacon design. All three Mango Beacons feature high contrasts and low costs when compared to conventional molecular beacons, with excellent potential for in vitro and in vivo applications.

Organic Photothermal Materials Obtained Using Thermally Activated Delayed Fluorescence Design Principles.

Organic small molecules with high photothermal conversion efficiencies that absorb near-infrared light are desirable for photothermal therapy due to their improved biocompatibility compared to inorganic materials and their ability to absorb light in the biological transparency window (650-1350 nm). Here we report three donor-acceptor organic materials DM-ANDI, O-ANDI, and S-ANDI that show high photothermal conversion efficiencies of 46-68 % with near-infrared absorption. The design of these molecules is based on the rational modification of a thermally activated delayed fluorescence material to favour a low photoluminescence quantum yield by reducing HOMO-LUMO overlap. Encapsulating these materials into either neat nanoparticles or aggregated organic dots modulates their photothermal conversion efficiencies, and also facilitates dispersion in water.