RRC ID 73728
著者 Morihiro K, Osumi H, Morita S, Hattori T, Baba M, Harada N, Ohashi R, Okamoto A.
タイトル Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly.
ジャーナル J Am Chem Soc
Abstract 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.
巻・号 145(1)
ページ 135-142
公開日 2023-1-11
DOI 10.1021/jacs.2c08974
PMID 36538570
MeSH Antineoplastic Agents* Biosensing Techniques* DNA Immunity, Innate MicroRNAs* / genetics Nucleic Acids*
IF 14.612
リソース情報
ヒト・動物細胞 HeLa(RCB0007) A549(RCB0098) B16 melanoma(RCB1283) RCB293T(RCB2202)