Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly

Artificial nucleic acids have attracted much attention as potential cancer immunotherapeutic materials because they are recognized by a variety of extracellular and intracellular nucleic acid sensors and can stimulate innate immune responses. However, their low selectivity for cancer cells causes severe systemic immunotoxicity, making it difficult to use artificial nucleic acid molecules for immune cancer therapy. To address this challenge, we herein introduce a hairpin DNA assembly technology that enables cancer-selective immune activation to induce cytotoxicity. The designed artificial DNA hairpins assemble into long nicked double-stranded DNA triggered by intracellular microRNA-21 (miR-21), which is overexpressed in various types of cancer cells. We found that the products from the hairpin DNA assembly selectively kill miR-21-abundant cancer cells in vitro and in vivo based on innate immune activation. Our approach is the first to allow selective oncolysis derived from intracellular DNA self-assembly, providing a powerful therapeutic modality to treat cancer.

Automated summary

Artificial nucleic acids have been widely studied as potential cancer immunotherapeutic materials due to their ability to stimulate innate immune responses. However, their low selectivity for cancer cells limits their effectiveness. In this study, a hairpin DNA assembly technology is introduced to selectively activate immune responses in cancer cells that overexpress miR-21, leading to cytotoxicity. This approach provides a novel therapeutic modality for cancer treatment through selective intracellular DNA self-assembly.