Fudan University Shanghai Cancer Center, and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Fudan University, Shanghai, 200032, China.
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
Adv Healthc Mater. 2018 Oct;7(20):e1701153. doi: 10.1002/adhm.201701153. Epub 2018 Jan 22.
In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life-threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine-phosphate-guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat-Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure-based systems for the delivery of therapeutic oligonucleotides are discussed.
在 21 世纪初，治疗性寡核苷酸在治疗许多危及生命的疾病方面显示出巨大的潜力。然而，将治疗性寡核苷酸有效递送到体内的靶向位置仍然是一个主要问题。作为一个新兴领域，DNA 纳米技术在生物成像、生物传感和药物输送等多个方面得到了应用。通过序列编程和优化，可以精确设计一系列具有确定大小、形状、表面化学性质和功能的 DNA 纳米结构。通过杂交，包括未甲基化的胞嘧啶-磷酸-鸟嘌呤二核苷酸寡核苷酸、小干扰 RNA（siRNA）或反义 RNA、规律间隔短回文重复 -Cas9 系统的单指导 RNA 和适体在内的治疗性寡核苷酸可成功负载在 DNA 纳米结构上进行递药。在本进展报告中，首先介绍了 DNA 纳米技术的发展历史，然后讨论了 DNA 纳米结构的细胞摄取机制和手段。接下来，总结了使用 DNA 纳米载体递送治疗性寡核苷酸的当前方法。最后，讨论了基于 DNA 纳米结构的系统递送治疗性寡核苷酸的挑战和机遇。
