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TLR8 Agonist - HIV-1 LTR-derived ssRNA / LyoVec™

ssRNA40 is a 20-mer phosphorothioate protected single-stranded RNA oligonucleotide containing a GU-rich sequence.

ssRNA40, also known as R-1075, is a U-rich single-stranded RNA derived from the HIV-1 long terminal repeat.

ssRNA40 is complexed with the cationic lipid LyoVec™, to protect it from degradation and facilitate its uptake.

Specifications

Specificity: human TLR8/mouse TLR7 agonist

Working Concentration: 0.25-5 μg/ml

Sequence: ssRNA40 5’-GsCsCsCsGsUsCsUsGsUsUsGsUsGsUsGsAsCsUsC-3’
(“s" depicts a phosphothioate linkage)

Solubility: 0.05 mg/ml in water

Contents

• 4x 25 μg lyophilized ssRNA40/LyoVec™ 1:2 ratio (w/w)

Note: Each vial contains 25 μg of ssRNA40 complexed with 50 μg LyoVec™.

• 10 ml endotoxin-free water

 ssRNA40/LyoVec™ is provided lyophilized and shipped at room temperature.

 Store at -20 ̊C.

 Lyophilized product is stable 1 year at -20 ̊C.

Upon resuspension, store product at 4°C. Resuspended product is stable 1 week at 4°C.

Description

ssRNA40 is a 20-mer phosphothioate protected single-stranded RNA oligonucleotide containing a GU-rich sequence [1].

ssRNA40 is complexed with the cationic lipid LyoVec™, to protect it from degradation and facilitate its uptake, and lyophilized to generate ssRNA40/LyoVec™. When complexed to cationic lipids, ssRNA can substitute for viral RNAs in inducing TNF-α and IFN-α production in peripheral blood mononuclear cells [1, 2].

Murine dendritic cells deficient for TLR7 failed to produce IFN-α in response to ssRNA40, while the response to CpG-ODNs was unaffected, suggesting that TLR7 plays a critical role in viral ssRNA recognition [1].

In human cells, TLR8 was shown to be the key receptor for viral ssRNA, implying a species specificity difference in ssRNA recognition.

During infection, some viral particles are degraded by the endosomal proteases, exposing the viral genome and allowing TLR7 and/or TLR8 signaling, which are known to occur in endosomes [3].

TLR7 and TLR8 can recognize both self and viral RNA but seem able to distinguish the presence of viral RNA by detecting their abnormal localization in the endosome rather than a particular RNA motif.

1. Heil F. et al., 2004. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 5;303(5663):1526-9.
2. Diebold SS. et al., 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 5;303(5663):1529-31
3. Heil F. et al., 2003 The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur J Immunol. 33(11):2987-97.

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