Capturing intracellular oncogenic microRNAs with self-assembled DNA nanostructures for microRNA-based cancer therapy

Abstract

Aberrantly overexpressed oncogenic microRNAs (miRNAs, miRs) are excellent targets for therapeutic interventions. Nevertheless, thus far, little progress has been made in developing miRNA-based drugs and techniques for clinical applications, especially for overexpressed miRNAs. In this study, we demonstrate that self-assembled DNA nanostructures bearing multiple DNA sequences that are complementary to a target miRNA can effectively capture the overexpressed oncogenic miRNA and subsequently inhibit cancer cell proliferation. Specifically, a DNA nanotube structure that carries functional DNA segments (single-stranded, duplex and hairpin forms) was designed and synthesized to capture two well-known overexpressed miRNAs, miR-21 and miR-155. It was found that all three DNA nanotubes significantly reduced both miRNA levels and inhibited cancer cell growth. Moreover, the capture efficiency was highly concentration dependent and was associated with the structural design of the DNA nanotube. These results demonstrate that through careful design, programmable DNA nanostructures can hijack the natural cellular machinery and can serve as nucleic acid drugs themselves. The concept of using self-assembled DNA nanostructures to disrupt the intracellular machinery for therapeutic purposes opens a new paradigm for exploiting self-assembled DNA nanostructures for miRNA-based anticancer therapy.