A Mirror Image Fluorogenic Aptamer Sensor for Live-Cell Imaging of MicroRNAs uri icon

abstract

  • Development of biocompatible tools for intracellular imaging of RNA expression remains a central challenge. Herein, we report the use of heterochiral strand-displacement to sequence-specifically interface endogenous d-miRNAs with an l-RNA version of the fluorogenic aptamer Mango III, thereby generating a novel class of biocompatible miRNA sensors. Fluorescence activation of the sensor is achieved through the displacement of an achiral blocking strand from the l-Mango aptamer by the d-RNA target. In contrast to d-Mango, we show that the l-Mango sensor retains full functionality in serum, enabling a light-up fluorescence response to the target. Importantly, we employ a self-delivering version of the l-Mango sensor to image the expression of microRNA-155 in living cells, representing the first time l-oligonucleotides have been interfaced with a living system. Overall, this work provides a new paradigm for the development of biocompatible hybridization-based sensors for live-cell imaging of RNAs and greatly expands the utility of fluorogenic aptamers for cellular applications.

altmetric score

  • 1

author list (cited authors)

  • Zhong, W., & Sczepanski, J. T.

citation count

  • 27

complete list of authors

  • Zhong, Wenrui||Sczepanski, Jonathan T

publication date

  • January 2019