Hybridization-based probes have been utilized to detect or monitor gene expression in cells. However, methods that use natural nucleic acids suffer from several limitations, including enzymatic degradation and off-target interactions. Herein, we show a new paradigm for overcoming these challenges using L-nucleic acids (L-DNA and L-RNA), which are mirror image (or enantiomers) of natural D-nucleotides. Nucleic acid enantiomers share the same physical and chemical properties, yet L-oligonucleotides are resistant to nuclease degradation and off-target interactions. These properties make L-oligonucleotides advantageous for <i>in vivo</i> applications. On this basis, we developed a fluorogenic aptamer-base sensor comprised of L-nucleic acids that is able to detect microRNA overexpression in living cells. An achiral nucleic acid blocking strand was used to prevent folding of the fluorogenic aptamer prior to its displacement by the endogenous D-microRNA target, which in turn results in the generation of a fluorescent signal. Details regarding this novel sensor will be presented.

Mirror image fluorogenic aptamer sensor for live-cell imaging of microRNAs

2019 Fall National Meeting

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