Antisense and siRNA as agonists of Toll-like receptors
Antisense and siRNA as agonists of Toll-like receptors
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DOI：
10.1038/nbt1042
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发表时间：
2004-12-01
影响因子：
46.9
通讯作者：
Kandimalla, ER
中科院分区：
文献类型：
--
作者：
Agrawal, S;Kandimalla, ER
大约25年前，研究人员首次证明了一种短的合成寡脱氧核苷酸，称为反义，可以通过与病毒RNA杂交来抑制劳斯肉瘤病毒的复制。从那时起，已经开发了几种基于杂交的寡核苷酸方法来阐明基因的功能及其作为治疗剂的潜力。短干扰RNA（S1）是最新的例子。为了有效抑制基因表达，反义或siRNA必须对核酸酶具有抗性，被细胞有效吸收，与靶mRNA有效杂交并激活靶mRNA的选择性降解或阻断其翻译而不引起不希望的副作用。然而，反义和siRNA试剂都已显示出发挥非靶标相关的生物学效应，包括免疫刺激。反义和siRNA药物是否作为Toll样受体（TLR）的配体发挥作用，TLR是一种病原体相关的分子模式识别受体家族？
About 25 years ago, researchers first demonstrated that a short synthetic oligodeoxynucleotide, referred to as antisense, can inhibit replication of Rous sarcoma virus through hybridization to viral RNA. Since then, several hybridization-based oligonucleotide approaches have been developed to elucidate the functions of genes and their potential as therapeutic agents. Short-interfering (si) RNA is the most recent example. To effectively inhibit gene expression, an antisense or siRNA must be resistant to nucleases, be taken up efficiently by cells, hybridize efficiently with the target mRNA and activate selective degradation of the target mRNA or block its translation without causing undesirable side effects. However, both antisense and siRNA agents have been shown to exert non-target-related biological effects including immune stimulation. Do antisense and siRNA agents work as ligands for Toll-like receptors (TLRs), a family of pathogen-associated, molecular pattern recognition receptors?