RNA:DNA Hybrid Agonist

RNA:DNA Hybrid

Cat. Num. AAA584790

• Applications: Functional Studies
• Synonyms: RNA:DNA Hybrid; RNA:DNA hybrids; RNA:DNA Hybrid agonist

• Form/Format: Approximately 5 nmol lyophilized and purified 60-mer RNA:DNA hybrids.

• Applicable Applications for RNA:DNA Hybrid agonist: Functional Studies
• Application Notes: RNA: DNA hybrids can be used for cellular stimulation. Furthermore, RNA:DNA hybrids can be used to induce a pro-inflammatory cytokine response in dendritic cells.
• Endotoxin: Endotoxin levels are undetectable.
• Reconstitution: Reconstitute the vial by pipetting nuclease-free water, volume depending on the concentration to be used.
• Preparation and Storage: Should be stored at 4 degree C. Store stock solution in aliquots at -20 degree C. Repeated freeze and thaw cycles will cause loss of activity.; Under recommended storage conditions, product is stable for at least one year.

Related Product Information for RNA:DNA Hybrid agonist

RNA:DNA hybrid represents a novel class of high-affinity ligand for Toll Like Receptor-9 (TLR9). TLRs are expressed by various cells of the immune system, such as macrophages and dendritic cells. TLRs are class I receptors, with a single alpha-helix that spans the cell membrane. They recognize and respond to molecules derived from bacterial, viral and fungal pathogens, such as lipopolysaccharide (LPS) from the outer membrane of Gram negative bacteria, peptidoglycan fragments from bacterial cell walls and single-stranded and double-stranded RNA from viruses. Nucleic acids are of course fundamental components of all pathogens. Several nucleic acid recognizing Pattern Recognition Receptors (PRR) have been identified including TLR3 (dsRNA), TLR7 (ssRNA), TLR8 (ssRNA), TLR9 (bacterial DNA) and TLR13 (23S rRNA) confined to the endosomal compartments, membrane bound C-type lectin receptors, the cytosolic Nod-like receptors and cytosolic RIG-like receptors. Nucleic acid binding to TLRs recruits the adaptor proteins TRIF or MyD88 to trigger NF-kappaB and/or IRF signaling pathways, inducing pro-inflammatory cytokines and type I interferons. Current understanding of TLR9 is primarily determined from the use of synthetic oligodeoxynucleotides. Most well-known is the interaction of TLR9 with non-methylated cytosineguanosine (CpG) motifs in DNA. Activation of TLR9 is ascribed to the detection of CpG-motifs within pathogen derived DNA. TLR9 signaling not only initiates innate immune cells, but also acquired responses. RNA:RNA hybrids have been described as a new ligand for TLR9. Many pathogenic viruses replicate via a RNA:DNA hybrid intermediate within the cell. Viral genomes are detected as non-self and induce a powerful antiviral response via type I interferon. Indeed, RNA:DNA hybrids are sensed by dendritic cells via TLR9. It was demonstrated that TLR9 mediated cytokine response elicit by the hybrid was MyD88 dependent. The ability to modulate TLR9 activity and subsequent innate responses, through DNA-based immunotherapeutics has been the focus of many research projects. Nucleic acids are attractive as therapeutics for their chemical stability and low costs. The ability to regulate downstream signaling by varying the sequences of the synthetic nucleic acid opens an interesting therapeutic window. HC4072 consists of a RNA:DNA hybrid duplex: 60-mer RNA(GU) annealed to 60-mer DNA (CA).

Product Categories/Family for RNA:DNA Hybrid agonist

Infectious Diseases

References

1. Kailasan Vanaja, S et al; Bacterial RNA:DNA hybrids are activators of the NLRP3 inflammasome. PNAS 2014, 111:7765. 2. Mankan, A et al; Cytosolic RNA:DNA hybrids activate the cGAS-STING axis. The EMBO J 2014, 33:2937. 3. Rigby, A et al; RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. The EMBO Journal 2014, 33:6. 4. Mackenzie, K et al; Ribonuclease H2 mutations induce a cGAS/STINGdependent innate immune response. The EMBO J 2016.