RLR Ligands Rationally Design

RLR receptors can detect the presence of RNA. RLR Ligand, polyribosinic:polyribocytidic acid (Poly I:C), can be recognized not only by RLR but also by TLR3. It can mimic viral infections and elicits host immune responses by triggering specific pattern recognition receptors. Creative Biolabs is a world leader in the field of vaccine development who has focused on the cancer vaccines for years. The extensive experience and expertise of our scientists enable Creative Biolabs to provide innate immune stimulators related development services, especially RLR ligands rationally design.

Retinoic Acid-inducible Gene I (RIG-1)-like Receptors (RLRs)

RIG-I-like receptors (retinoic acid-inducible gene-I-like receptors, or RLRs), a family of cytosolic PRRs that activate the inflammasome, are cytoplasmic RNA sensors containing caspase activation and recruitment domains and can detect the presence of RNA from a broad range of viruses by the innate immune system. There are three types of RLRs, including RIG-I, MDA5, and LGP2, of which RIG-I was the first to be discovered. All these three receptors have a DExD/H box helicase structure and are located in tissues throughout the body. RLR is particularly active in the innate immune defense of epithelial cells, bone marrow cells, and CNS cells. RLRs are present in the cytosol of cells as pattern recognition receptors, so they can detect the presence of viral DNA or RNA. After detection of viral infection, RIG-I and MDA5 have the ability to activate complex signaling networks that result in the production of pro-inflammatory molecules. RIG-I and MDA5 recognize different viruses, but all produce antiviral immunity changes, triggering innate responses and modulating subsequent adaptive responses. The remaining RLR, LGP2, lacks the ability to induce signaling alone but is required for efficient RIG-I and MDA5 mediated antiviral responses.

Synthetic double-stranded RNA (dsRNA), Poly I:C can be recognized by and TLR3. Delivery of poly I:C liposomes to melanoma cells has been reported to cause IPS1- and type 1 IFN-dependent apoptosis in vitro and in vivo.

Overview of RLRs signaling pathway.

Fig.1 Overview of RLRs signaling pathway. (Jin HS. 2017)

RLR Ligands

Poly I:C is one of the synthetic dsRNA molecules that activate innate and adaptive immune components. It mimics viral infections and elicits host immune responses by triggering specific pattern recognition receptors (PRRs). Poly-IC signals primarily through MDA-5 (cytoplasmic receptor) and TLR3 (transmembrane and most endosomal receptor). The derivatives of Poly(I:C) are also effective adjuvants, such as poly-IC12U and poly-ICLC, of which the mechanisms and potency of immune activation are not identical. Poly I:C and its derivatives have been used as vaccine adjuvants for cancer immunotherapy for decades, based on their ability to enhance innate immunity and adapt to immune responses and alter the tumor microenvironment. These synthetic immune risk signals enhance vaccine-induced anti-tumor immune responses and contribute to tumor elimination in animal tumor models and patients.

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

Reference

  1. Jin HS, et al. Mitochondrial Control of Innate Immunity and Inflammation. Immune Netw. 2017, 17(2): 77-88.

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