Qian H, Tay C Y, Setyawati M I, Chia S L, Lee D S, Leong D T
Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585 , Singapore . Email:
Institute of Respiratory Diseases and Critical Care , Xinqiao Hospital of Third Military Medical University , 183 Xinqiao Street , Chongqing 400037 , China.
Chem Sci. 2017 Feb 1;8(2):1062-1067. doi: 10.1039/c6sc01829g. Epub 2016 Sep 14.
Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA-DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy.
肿瘤抑制性微小RNA是一种强大的分子，有望在未来某一天治愈癌症。尽管有许多将这些微小RNA递送至细胞的先进策略，但临床应用中的治疗性微小RNA却很少。微小RNA生物应用的进展受到外源性微小RNA分子在细胞外和细胞内生理条件下极易被核糖核酸酶降解的阻碍。在这项概念验证研究中，我们使用了一种具有“手里剑”形状的可编程自组装DNA纳米结构，不仅用于递送，更重要的是长时间保护肿瘤抑制性微小RNA-145，使其在人结肠癌细胞中发挥治疗作用。我们的DNA纳米结构含有可与微小RNA货物杂交的互补序列。这使得微小RNA-DNA双链非常接近核心结构，从而使微小RNA货物在空间上免受核糖核酸酶降解活性的影响。我们基于新型DNA纳米结构的保护概念消除了可能困扰其他核酸递送策略的降解瓶颈，并为利用这些微小RNA进行抗癌治疗提供了一种新的范例。
