Single-stranded circular DNA theranostics.
Single-stranded circular DNA theranostics.
复制标题
单链环状 DNA 治疗诊断学
作者：
Shen T;Zhang Y;Mei L;Zhang XB;Zhu G
过去十年见证了核酸治疗和诊断（治疗诊断学）的开花。与传统的小分子药物或蛋白质生物制剂不同，核酸治疗诊断剂具有特征性特征，例如作为“信息药物”编码和执行遗传和治疗诊断信息的固有能力、核酸工程的现成可编程性、内在刺激性或调节性免疫调节、多功能性以及在热或化学变性时容易的构象恢复。单链环状DNA（Single-stranded circular DNA，circDNA）是一类具有共价闭合拓扑结构的单链DNA（single-stranded DNA，ssDNA）。除了基于核酸的材料的基本优点之外，例如低成本、生物相容性和化学修饰的简单性，circDNA中末端的缺乏防止了外切核酸酶降解，导致相对于相应的线性ssDNA的增强的生物稳定性。circDNA已被探索用于多功能治疗诊断应用。例如，circDNA已被广泛研究为用于生物分析信号放大和经由滚环扩增（RCA）和滚环转录（RCT）技术合成纳米/微米/宏观生物材料的模板。circDNA也常用作多功能DNA“折纸”自组装的支架。最后，circDNA已被用作治疗诊断适体、miRNA抑制剂以及成簇的规则间隔短回文重复序列-CRISPR相关蛋白（CRISPR-Cas）基因编辑供体。在这篇综述文章中，我们将讨论circDNA（不包括双链环状DNA，如质粒）的化学，特征性质和治疗诊断应用，我们也将展望在这一研究领域的挑战和机遇。
The past decade has witnessed the blossom of nucleic acid therapeutics and diagnostics (theranostics). Unlike conventional small molecule medicines or protein biologics, nucleic acid theranostics have characteristic features such as the intrinsic ability as “information drugs” to code and execute genetic and theranostic information, ready programmability for nucleic acid engineering, intrinsic stimulatory or regulatory immunomodulation, versatile functionalities, and easy conformational recovery upon thermal or chemical denaturation. Single-stranded circular DNA (circDNA) are a class of single-stranded DNAs (ssDNA) featured with their covalently-closed topology. In addition to the basic advantages of nucleic acids-based materials, such as low cost, biocompatibility, and simplicity of chemical modification, the lack of terminals in circDNA prevents exonuclease degradation, resulting in enhanced biostability relative to the corresponding linear ssDNA. circDNA has been explored for versatile theranostic applications. For instance, circDNA has been extensively studied as templates for bioanalytical signal amplification and the synthesis of nano-/micro-/macro- biomaterials via rolling circle amplification (RCA) and rolling circle transcription (RCT) technologies. circDNA has also been commonly used as the scaffolds for the self-assembly of versatile DNA origami. Finally, circDNA has been implemented as theranostic aptamers, miRNA inhibitors, as well as clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) gene editing donors. In this review article, we will discuss the chemistry, characteristic properties, and the theranostic applications of circDNA (excluding double-stranded circular DNA such as plasmids); we will also envision the challenges and opportunities in this research field.