摘要
寡核苷酸,如反义寡核苷酸、小干扰RNA、适配体等可通过靶向致病性的RNA或蛋白并抑制其活性而达到治疗疾病的目的,但是许多类型的寡核苷酸有着主动靶向性差、体内不稳定和跨膜能力差等缺点,因此研究人员通常在传统寡核苷酸的基础上,通过将寡核苷酸共价偶联其他功能分子的方法来改善核酸分子的功能及性质,如细胞摄取、组织传递效果、生物利用度、催化效果等,从而提高治疗性核酸的作用效果.针对寡核苷酸偶联物在递送和催化降解2个方向的发展,综述了7种典型的寡核苷酸偶联物的最新研究进展,旨在为寡核苷酸偶联物的结构设计与进一步临床应用提供思路和参考.
Abstract
Oligonucleotides such as antisense oligonucleotides(ASOs),small interfering RNA(siRNA)and aptamer can achieve the purpose of treating diseases by targeting pathogenic RNA or protein and inhibiting its activity,but many types of oligonucleotides have such disadvantages as poor active targeting,instability in vivo and poor transmembrane ability,so on the basis of traditional oligonucleotides,the functions and properties of nucleic acid molecules are improved by covalently coupling oligonucleotides with other functional molecules,e.g.,improving cell uptake,tissue delivery,bioavailability,catalytic effect,etc.,and thereby improving the effect of therapeutic nucleic acid.This article focuses on the development of oligonucleotide conjugates in two directions of delivery and catalytic degradation,and reviews the latest research progress of 7 typical oligonucleotide conjugates,so as to provide some insights and reference for structural design and further clinical application of oligonucleotide conjugates.
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