Cellular uptake and trafficking of antisense oligonucleotides

被引：441

作者：

Crooke, Stanley T. ^{[1
]}

Wang, Shiyu ^{[1
]}

Vickers, Timothy A. ^{[1
]}

Shen, Wen ^{[1
]}

Liang, Xue-hai ^{[1
]}

机构：

[1] Ionis Pharmaceut Inc, Dept Core Antisense Res, Carlsbad, CA 92010 USA

来源：

NATURE BIOTECHNOLOGY | 2017年 / 35卷 / 03期

关键词：

PHOSPHOROTHIOATE OLIGONUCLEOTIDES; INTRACELLULAR TRAFFICKING; SIRNA OLIGONUCLEOTIDES; MEDIATED ENDOCYTOSIS; TARGETED DELIVERY; MAMMALIAN-CELLS; CATIONIC LIPIDS; NUCLEAR-BODIES; PROTEIN; RECEPTOR;

D O I：

10.1038/nbt.3779

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2' modifications can be used either as drugs (e.g., to treat homozygous familial hypercholesterolemia and spinal muscular atrophy) or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA (including mRNA and non-coding RNA) targeted by endogenous RNase H1. Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency. Cellular uptake and intracellular distribution of PS ASOs are mediated by protein interactions. The main proteins involved in these processes have been identified, and intracellular sites in which PS ASOs are active, or inactive, cataloged.

引用

页码：230 / 237

页数：8

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