Assessment of Intracellular Compartmentalization of RNA Nanostructures.
Assessment of Intracellular Compartmentalization of RNA Nanostructures.
复制标题
RNA 纳米结构细胞内区室化的评估。
DOI：
10.1007/978-1-0716-3417-2_14
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Johnson,MBrittany
中科院分区：
文献类型：
--
作者：
Radwan,Yasmine;Afonin,KirillA;Johnson,MBrittany
核酸纳米颗粒（NANP）作为诊断和治疗工具被广泛研究。这些创新的颗粒可以由RNA、DNA和/或修饰的核酸组成。由于核酸在细胞系统中的调节作用，NANP具有识别靶分子和调节疾病途径中基因表达的能力。然而，NANP在临床环境中的翻译由于低效的细胞内递送、化学不稳定性和免疫识别后的脱靶免疫刺激效应而受阻。已证明形成NANP的核酸的组成影响NANP的免疫识别、亚细胞区室化和物理化学性质。本章首先概述了用于生成具有统一形状、大小、电荷、序列和连接性的NANP面板的方法。这包括在指定的NANP中用DNA或化学类似物替换RNA链的程序。其次，本章还将描述实验来评估化学修饰对NANP的酶和热力学稳定性、递送效率和亚细胞区室化的影响。
Nucleic acid nanoparticles (NANPs) are extensively investigated as diagnostic and therapeutic tools. These innovative particles can be composed of RNA, DNA, and/or modified nucleic acids. Due to the regulatory role of nucleic acids in the cellular system, NANPs have the ability to identify target molecules and regulate expression of genes in disease pathways. However, translation of NANPs in clinical settings is hindered due to inefficient intracellular delivery, chemical instability, and off-target immunostimulatory effects following immune recognition. The composition of nucleic acids forming NANPs has been demonstrated to influence immunorecognition, subcellular compartmentalization, and physicochemical properties of NANPs. This chapter first outlines the methods used to generate a panel of NANPs with a uniform shape, size, charge, sequence, and connectivity. This includes the procedures for replacing the RNA strands with DNA or chemical analogs in the designated NANPs. Second, this chapter will also describe experiments to assess the effect of the chemical modification on enzymatic and thermodynamic stability, delivery efficiency, and subcellular compartmentalization of NANPs.