核酸
DNA
化学
溶瘤病毒
免疫系统
先天免疫系统
癌细胞
细胞内
癌症
小RNA
DNA损伤
细胞生物学
细胞毒性
体外
生物
生物化学
基因
免疫学
遗传学
作者
Kunihiko Morihiro,Hiraki Osumi,Shunto Morita,Takara Hattori,Manami Baba,Naoki Harada,Riuko Ohashi,Akimitsu Okamoto
摘要
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.
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