In mammalian cells, the presence of uncapped 5′-triphosphate (or diphosphate) groups on nucleic acids is a known PAMP, recognized in the cytosol by the RIG-I helicase as a probable viral infection and triggering a type I IFN inflammatory response.91, 92 Indeed, siRNA-3WJs retaining their 5′-triphosphate groups provoked a significant pro-inflammatory response in transfected astrocytes, evident as increased levels of Ifnb1, Il6, and Tnf. This effect was mirrored by significant increases in the quantity of secreted IL-6 and TNF-α upon transfection with phosphorylated siRNA-3WJs. Here, TNF is linked to viral infectious disease.