第二代反义寡核苷酸的研究

The Second Generation Antisense Oligonucleotides

第一代反义核酸寡核苷酸硫代磷酸酯，是目前研究最广泛、最成熟的反义核酸药物，已进入临床试验阶段，但其具有一定的毒副作用；第二代反义核酸，包括嵌合寡核苷酸、杂合寡核苷酸等，是在硫代寡核苷酸的基础上，再引入其它的修饰基团，从而提高其生物活性，减少毒副作用。本文着重介绍了第二代反义核酸的生物物理学性质，药动学及其与第一代反义核酸毒性的比较。

The first generation oligonucleotides phosphorothiate oligonucleotides have been the most widely studied. Many of them are currently in clinical trials. But they also have certain side effects. The second generation oligonucleotides,including chimeric oligonucleotides and hybrid oligonucleotides,contain phosphorothiate linkages while other chemical modifications are introduced to different sites,and therefore generate a favorable pharmacological and safety profile.This article focuses on the biophysical properties and pharmacokinetics of second generation antisense oligonucleotides, and makes a comparison between the two generations antisense of oligonucleotides in adverse reaction.