Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5′ phosphates. A few reports of 5′-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found that the bent duplex RNA from the influenza A panhandle promoter activates RIG-I even in the absence of a 5′-triphosphate moiety. Here, we report that non-canonical synthetic RNA oligonucleotides containing G-U wobble base pairs that form a bent helix can exert RIG-I-mediated antiviral and anti-tumor effects in a sequence- and site-dependent manner. We present synthetic RNAs that have been systematically modified to enhance their efficacy and we outline the basic principles for engineering RIG-I agonists applicable to immunotherapy.

中文翻译：

---

合成RIG-I配体的系统编辑，以产生有效的抗病毒和抗肿瘤RNA免疫疗法

维甲酸诱导基因I（RIG-I）识别包含两个或三个5'磷酸的双链病毒RNA（dsRNA）。已经出现了一些关于5'-PPP无关的RIG-I激动剂的报道，但对于识别它们的分子原理知之甚少。我们最近发现，即使在没有5'-三磷酸部分的情况下，来自甲型流感泛把手启动子的弯曲双链RNA也会激活RIG-I。在这里，我们报告包含形成弯曲螺旋的GU摆动碱基对的非规范合成RNA寡核苷酸可以序列和位点依赖的方式发挥RIG-I介导的抗病毒和抗肿瘤作用。我们提出了经过合成修饰以增强其功效的合成RNA，并概述了适用于免疫疗法的RIG-I激动剂工程化的基本原理。