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.