Abstract：
Oligonucleotide-based therapeutics have attracted attention as an emerging modality that includes the modulation of genes and their binding proteins related to diseases, allowing us to take action on previously undruggable targets. Since the late 2010s, the number of oligonucleotide medicines approved for clinical uses has dramatically increased. Various chemistry-based technologies have been developed to improve the therapeutic properties of oligonucleotides, such as chemical modification, conjugation, and nanoparticle formation, which can increase nuclease resistance, enhance affinity and selectivity to target sites, suppress off-target effects, and improve pharmacokinetic properties. Similar strategies employing modified nucleobases and lipid nanoparticles have been used for developing coronavirus disease 2019 mRNA vaccines. In this review, we provide an overview of the development of chemistry-based technologies aimed at using nucleic acids for developing therapeutics over the past several decades, with a specific emphasis on the structural design and functionality of chemical modification strategies.
摘要：
基于寡核苷酸的疗法作为一种新兴的方式引起了人们的关注，包括调节与疾病相关的基因及其结合蛋白，允许我们对以前无法下药的目标采取行动.自2010年代后期以来，批准用于临床用途的寡核苷酸药物的数量急剧增加。已经开发了各种基于化学的技术来改善寡核苷酸的治疗特性，如化学改性，共轭，和纳米粒子的形成，可以增加核酸酶抗性，增强对靶位点的亲和力和选择性，抑制脱靶效应，并改善药代动力学特性。采用修饰的核碱基和脂质纳米颗粒的类似策略已用于开发冠状病毒病2019mRNA疫苗。在这次审查中,我们概述了过去几十年来旨在使用核酸开发疗法的基于化学的技术的发展，特别强调化学改性策略的结构设计和功能。
