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Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2022-12-20 , DOI: 10.1021/jacs.2c08974 Kunihiko Morihiro 1 , Hiraki Osumi 1 , Shunto Morita 1 , Takara Hattori 1 , Manami Baba 1 , Naoki Harada 1 , Riuko Ohashi 2, 3 , Akimitsu Okamoto 1
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2022-12-20 , DOI: 10.1021/jacs.2c08974 Kunihiko Morihiro 1 , Hiraki Osumi 1 , Shunto Morita 1 , Takara Hattori 1 , Manami Baba 1 , Naoki Harada 1 , Riuko Ohashi 2, 3 , Akimitsu Okamoto 1
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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.
中文翻译：
溶瘤发夹 DNA 对：通过 MicroRNA 触发的 DNA 自组装的选择性细胞毒性诱导剂
人工核酸作为潜在的癌症免疫治疗材料备受关注，因为它们被多种细胞外和细胞内核酸传感器识别并可以刺激先天免疫反应。然而，它们对癌细胞的低选择性会导致严重的全身免疫毒性，使得人工核酸分子难以用于免疫癌症治疗。为了应对这一挑战，我们在此介绍了一种发夹 DNA 组装技术，该技术能够使癌症选择性免疫激活来诱导细胞毒性。设计的人工 DNA 发夹组装成由细胞内 microRNA-21 (miR-21) 触发的长切口双链 DNA，它在各种类型的癌细胞中过表达。我们发现来自发夹 DNA 组装的产物基于先天免疫激活，在体外和体内选择性地杀死 miR-21 丰富的癌细胞。我们的方法是第一个允许从细胞内 DNA 自组装衍生的选择性溶瘤，为治疗癌症提供了一种强大的治疗方式。
更新日期：2022-12-20
中文翻译：
溶瘤发夹 DNA 对：通过 MicroRNA 触发的 DNA 自组装的选择性细胞毒性诱导剂
人工核酸作为潜在的癌症免疫治疗材料备受关注，因为它们被多种细胞外和细胞内核酸传感器识别并可以刺激先天免疫反应。然而，它们对癌细胞的低选择性会导致严重的全身免疫毒性，使得人工核酸分子难以用于免疫癌症治疗。为了应对这一挑战，我们在此介绍了一种发夹 DNA 组装技术，该技术能够使癌症选择性免疫激活来诱导细胞毒性。设计的人工 DNA 发夹组装成由细胞内 microRNA-21 (miR-21) 触发的长切口双链 DNA，它在各种类型的癌细胞中过表达。我们发现来自发夹 DNA 组装的产物基于先天免疫激活，在体外和体内选择性地杀死 miR-21 丰富的癌细胞。我们的方法是第一个允许从细胞内 DNA 自组装衍生的选择性溶瘤，为治疗癌症提供了一种强大的治疗方式。
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