Hornung Veit, Barchet Winfried, Schlee Martin, Hartmann Gunther
Institute of Clinical Biochemistry and Pharmacology, University Hospital , University of Bonn, Germany.
Handb Exp Pharmacol. 2008(183):71-86. doi: 10.1007/978-3-540-72167-3_4.
In this chapter we focus on immunorecognition of RNA by two members of the family of Toll-like receptors (TLRs), TLR7, and TLR8. While any long single-stranded RNA is readily recognized by both TLR7 and TLR8, sequencedependent activation of TLR7 and TLR8 becomes more evident when using short RNA oligonucleotides. RNA oligonucleotides containing sequence motifs for TLR7 and TLR8 are termed is RNA (immunostimulatory RNA). Moreover, short doublestranded RNA oligonucleotides as used for siRNA (short interfering RNA) containing such sequences function primarily as ligands for TLR7 but not TLR8. Even in the presence of appropriate sequence motifs, RNA is not detected by TLR7 and TLR8 when certain chemical modifications are present. Both immunological recognition and ignorance are relevant for the development of RNA-based therapeutics, depending on the clinical setting for which they are developed.
在本章中，我们将重点关注Toll样受体（TLR）家族的两个成员TLR7和TLR8对RNA的免疫识别。虽然任何长链单链RNA都能被TLR7和TLR8轻易识别，但在使用短RNA寡核苷酸时，TLR7和TLR8的序列依赖性激活变得更加明显。含有TLR7和TLR8序列基序的RNA寡核苷酸被称为免疫刺激RNA（isRNA）。此外，用于小干扰RNA（siRNA）的含有此类序列的短双链RNA寡核苷酸主要作为TLR7的配体，而非TLR8的配体。即使存在适当的序列基序，当存在某些化学修饰时，TLR7和TLR8也无法检测到RNA。免疫识别和免疫忽视对于基于RNA的治疗药物的开发都很重要，这取决于它们所针对的临床环境。
