K. Afonin, M. Jones
University of North Carolina, Charlotte,
Keywords: RNA interference, quantum dors, RNA nanotechnology
Summary:The mechanism of conventional therapeutics frequently combines two steps: a diagnosis, through binding to a specific biomarker, and a treatment, through inhibiting biomarker’s function. While this approach is successful, more therapeutic options become available if the diagnosis and treatment steps are not separated. Theranostic probes have been developed to combine together the therapeutic and diagnostic techniques by integrating both drug and imaging agents into the same construct. Our recent invention introduced a novel technique based on RNA-DNA hybrids with split-functionalities (e.g. multiple split siRNAs, aptamers, and FRET), which are only activated when two complementary copies are introduced into the same cell. Strand exchange is promoted by the interaction of complementary single-stranded DNA toeholds, and the functionalities are then activated intracellularly. We further expanded this idea with the simultaneous delivery and release of multiple functionalities, by including, for example, up to seven multiple anti-cancer split siRNAs into one hybrid duplex or RNA-DNA based nanoparticles. Here, we combined the unique properties of RNA-DNA hybrid technique and fluorescent non-toxic QDs to design various combinatorial and conditionally activated theranostic probes for a broad range of biomedical applications.