期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 59, 期 2-3, 页码 153-163出版社
ELSEVIER
DOI: 10.1016/j.addr.2007.03.006
关键词
RNA interference; small interfering RNAs; innate immunity; toll-like receptors; 2 '-ribose modifications; off-target effects
RNA interference is an evolutionarily conserved gene silencing process triggered by double-stranded RNAs. Common to all cell types, is the production of 21-24 nucleotide small interfering RNA (siRNAs), which guide the RNA-induced silencing complex (RISC) to identify and cleave target mRNA sequences. Presently, this biological breakthrough method has revolutionised gene function studies and holds great promise as validating drug targets and treating human diseases. However, despite the success that has been achieved by this technology, studies carried in human blood cells have revealed that siRNAs could generate bystander effects, including the activation of innate immunity and inhibition of unintended target genes. Interestingly, 2' uridine-modified siRNAs did not trigger TLR signalling, but they totally suppressed immune activation by immumostimulatory siRNAs when both molecules where delivered to the same endosomes. This review describes the recent advances in understanding the innate immune response to both single and double-stranded siRNAs. Also, it highlights the spectrum of molecular strategies allowing the design of therapeutic siRNAs with minimal side effects. (C) 2007 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据