Poly(dA:dT)

Synthetic analog of B-DNA

Poly(dA:dT) is a poly(deoxyadenylic-deoxythymidylic) acid sodium salt. It is a repetitive synthetic double-stranded DNA sequence of poly(dA-dT):poly(dT-dA) and a synthetic analog of B-DNA.

Poly(dA:dT) is recognized by multiple PRRs:

• Sensing by cytosolic DNA sensors (CDS), including cGAS, AIM2, DAI, DDX41, IFI16, and LRRFIP1, triggers the production of type I interferons [1-3].
• Sensing by the cytosolic DNA sensor AIM2 triggers the formation of an inflammasome and the subsequent secretion of IL-1β and IL-18 [4].
• Indirect sensing by the cytosolic RNA sensor RIG-I can occur upon the transcription of Poly(dA:dT) into dsRNA with a 5'triphosphate moiety (5'ppp-dsRNA) by the RNA polymerase III [5,6]. This indirect sensing by RIG-I leads to the production of type I interferons [7].

To achieve stimulation of cytosolic PRRs, Poly(dA:dT) must be delivered into the cytoplasm, for example by using a transfection agent, such as LyoVec™.

Key features of Poly(dA:dT):

• Poly(dA:dT) is a multi-PRR agonist.
• Its biological activity has been verified using our RLR reporter cell lines and Inflammasome Test Cells.
• For your convenience, pre-complexed Poly(dA:dT)/ LyoVec™ is also available.

References:

1. Unterholzner L., 2013. The interferon response to intracellular DNA: why so many receptors? Immunobiology. 218(11):1312-21.
2. Zhang Z. et al., 2011. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol. 12(10):959-65.
3. Wu J. et al., 2013. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 339(6121):826-30.
4. Jones JW. et al., 2010. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. PNAS, 107(21):9771-6.
5. Ablasser A. et al., 2009. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 10(10):1065-72.
6. Chiu YH. et al., 2009. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 138(3):576-91.
7. Takeshita F. & Ishii KJ., 2008. Intracellular DNA sensors in immunity. Curr Opin Immunol. 20(4):383-8.