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【Nature Biotechnology编译】科学家合成既能调整RN
Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA
来源
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nbt/journal/v23/n4/abs/nbt1081.html&dynoptions=doi1116247147
Nature Biotechnology 23, 457 - 462 (2005)
Published online: 20 March 2005; | doi:10.1038/nbt1081
原文
Short interfering RNAs (siRNAs) that mediate specific gene silencing through RNA interference (RNAi) are widely used to study gene function and are also being developed for therapeutic applications1. Many nucleic acids, including double- (dsRNA)2 and single-stranded RNA (ssRNA)3, 4, 5, can stimulate innate cytokine responses in mammals. Despite this, few studies have questioned whether siRNA may have a similar effect on the immune system6, 7. This could significantly influence the in vivo application of siRNA owing to off-target effects and toxicities associated with immune stimulation. Here we report that synthetic siRNAs formulated in nonviral delivery vehicles can be potent inducers of interferons and inflammatory cytokines both in vivo in mice and in vitro in human blood. The immunostimulatory activity of formulated siRNAs and the associated toxicities are dependent on the nucleotide sequence. We have identified putative immunostimulatory motifs that have allowed the design of siRNAs that can mediate RNAi but induce minimal immune activation.
编译
短干扰RNA（SiRNA）可以通过RNA干扰（RNAi）调节特异性的基因沉默，这广泛的用于研究基因功能，也在治疗方法研究中得到应用。很多核酸，包括双链RNA和单链RNA，可以刺激哺乳动物的内生细胞因子反应。尽管如此，很少有研究质疑是否SiRNA可能在免疫系统中具有类似作用。这篇论文作者研究了非病毒传输载体携带的合成SiRNA可以诱导产生干扰素和炎症细胞因子，不管是在鼠体内还是在人的体外血液中。这种SiRNA的免疫刺激活性和相关的毒性依赖于核酸序列。作者已经证实先前已知的免疫刺激基序可以使设计的SiRNA既能调整RNAi的作用，又能较少的诱导免疫活性。 能否提供原文 谢谢
afei wrote:
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作者:admin@医学,生命科学 2011-04-01 05:17
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