上海交通大学谭蔚泓团队报道了基于适体的功能核酸靶向递送。相关研究成果于2023年3月29日发表在《美国化学会杂志》。

基于功能核酸（NA）的药物具有广泛的应用，因为它们可以改变和控制细胞中的基因/蛋白质表达模式。原则上，功能性NA需要精确有效地输送到靶细胞，以保证功能性和安全性。由于其负电荷，天然NAs很难穿过由脂质双层组成的细胞膜进入靶细胞。更糟糕的是，向非靶向健康细胞和/或组织递送无定向功能性NAs会导致不可预测的不良反应。因此，需要将功能性NA精确靶向递送到特定的细胞/器官，特别是肝外部位。由于适体可以以高特异性和高选择性与细胞表面的各种蛋白质结合，因此它们可以作为分子识别单元准确结合靶细胞，从而实现货物的有效递送。

从这个角度来看，研究人员总结了最初的、基于概念验证的适体的功能性NA靶向递送策略。然后讨论了一些具体的例子，然后是我们对未来的一些挑战和机遇的看法。

附：英文原文

Title: Aptamer-Based Targeted Delivery of Functional Nucleic Acids

Author: Sitao Xie, Weidi Sun, Ting Fu, Xiangsheng Liu, Peng Chen, Liping Qiu, Fengli Qu, Weihong Tan

Issue&Volume: March 29, 2023

Abstract: Functional nucleic acid (NA)-based drugs have a broad range of applications since they allow the alteration and control of gene/protein expression patterns in cells. In principle, functional NAs need to be transported precisely and efficiently to target cells to guarantee both functionality and safety. Owing to their negative charges, it is difficult for natural NAs to cross the cell membrane composed of lipid bilayer and enter targeted cells. Worse still, the delivery of undirected functional NAs to nontargeted healthy cells and/or tissues would induce unpredictable adverse effects. Therefore, the precisely targeted delivery of functional NAs to specific cells/organs, particularly in extrahepatic sites, is required. Since aptamers can bind to various proteins on the cell surface with high specificity and selectivity, they can serve as the molecular recognition units to accurately bind target cells and subsequently enable the efficient delivery of cargo. In this perspective, we summarize the original, proof-of-concept aptamer-based strategies for the targeted delivery of functional NAs. A few specific examples are then discussed, followed by our perspectives on some of the challenges and opportunities that lie ahead.

DOI: 10.1021/jacs.3c00841

Source: https://pubs.acs.org/doi/10.1021/jacs.3c00841