PolyIC

Poly(I:C), short for polyinosinic-polycytidylic acid, is a synthetic double-stranded RNA analogue used to mimic viral infection in research and some clinical contexts. By resembling viral dsRNA, it stimulates innate immune pathways and can induce production of type I interferons and other cytokines. The molecule acts as a pathogen-associated molecular pattern that triggers several intracellular sensors, leading to antiviral states in cells.

Chemically, poly(I:C) is a heteropolymer composed of inosine and cytidine nucleotides linked in a double-stranded form. It is available in different molecular weight variants, ranging from low to high molecular weight, which influence the strength and profile of receptor engagement. Stabilized formulations exist to improve in vivo activity. A commonly used stabilized form is poly(I:C)LC, which is poly(I:C) complexed with poly-L-lysine and carboxymethylcellulose; this variant is sometimes marketed as Hiltonol or poly(ICLC). Variants and delivery methods are chosen to modulate immune activation and safety.

Mechanistically, poly(I:C) engages endosomal Toll-like receptor 3 (TLR3) and cytosolic RNA sensors such as MDA5 and, to a lesser extent, RIG-I. Activation of these pathways leads to signaling cascades that promote interferon regulatory factors, NF-κB, and the production of type I interferons and pro-inflammatory cytokines, creating an antiviral state and enhancing antigen presentation.

Applications include serving as an experimental tool to study innate immunity, acting as an adjuvant to boost vaccine responses, and exploring cancer immunotherapy and antiviral research. Safety concerns include its potential to provoke strong inflammatory reactions; systemic administration can cause fever and adverse cytokine effects, limiting clinical use to specific formulations and controlled settings.