RNAi 治疗药物的化学和结构修饰。

Chemical and structural modifications of RNAi therapeutics.

机构信息

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.

出版信息

Adv Drug Deliv Rev. 2016 Sep 1;104:16-28. doi: 10.1016/j.addr.2015.10.015. Epub 2015 Nov 5.

DOI:10.1016/j.addr.2015.10.015

PMID:26549145

Abstract

Small interfering RNA (siRNA), a 21-23nt double-stranded RNA responsible for post-transcriptional gene silencing, has attracted great interests as promising genomic drugs, due to its strong ability to silence target genes in a sequence-specific manner. Despite high silencing efficiency and on-target specificity, the clinical translation of siRNA has been hindered by its inherent features: poor intracellular delivery, limited blood stability, unpredictable immune responses and unwanted off-targeting effects. To overcome these hindrances, researchers have made various advances to modify siRNA itself and to improve its delivery. In this review paper, first we briefly discuss the innate properties and delivery barriers of siRNA. Then, we describe recent progress in (1) chemically and structurally modified siRNAs to solve their intrinsic problems and (2) siRNA delivery formulations including siRNA conjugates, polymerized siRNA, and nucleic acid-based nanoparticles to improve in vivo delivery.

摘要

小干扰 RNA（siRNA）是一种 21-23 个核苷酸的双链 RNA，可导致转录后基因沉默，由于其具有序列特异性沉默靶基因的强大能力，因此作为有前途的基因组药物引起了极大的关注。尽管 siRNA 具有很高的沉默效率和靶特异性，但由于其固有特性：细胞内递送效率低、血液稳定性有限、不可预测的免疫反应和不必要的脱靶效应，其临床转化受到了阻碍。为了克服这些障碍，研究人员在修饰 siRNA 本身和改善其递送方面取得了各种进展。在这篇综述论文中，我们首先简要讨论了 siRNA 的先天特性和递送障碍。然后，我们描述了最近在（1）化学和结构修饰的 siRNA 以解决其内在问题和（2）siRNA 递药制剂方面的进展，包括 siRNA 缀合物、聚合的 siRNA 和基于核酸的纳米颗粒以改善体内递送。