ADU-S100 VacciGrade™ - STING-based Adjuvant

c-di-AMP bisphosphorothioate (Rp,Rp) – Th1/Th2 response adjuvant

2’3’-c-di-AM(PS)₂ (Rp,Rp) is the Rp, Rp-isomer of the 2’3’ bisphosphorothioate analog of 3’3’-cyclic adenosine monophosphate (c-di-AMP), a  cyclic dinucleotide (CDN). c-di-AMP is a second messenger molecule produced by bacteria and has potent immunostimulant activity in mammals [1]. It activates innate immunity by directly binding the endoplasmic reticulum-resident receptor STING (stimulator of interferon genes), leading to the expression of interferon-β (IFN-β) and nuclear factor-κB (NF-κB) dependent inflammatory cytokines [2].

Key Features

• 2’3’-c-di-AM(PS)₂ (Rp,Rp) has a higher affinity for STING than c-di-AMP due to the presence of a 2’-5’, 3’-5’ mixed linkage, as found in endogenous human CDNs produced by cGAS (cyclic GMP-AMP (cGAMP) synthase) [3]. It activates all known human STING alleles, as well as mouse STING.
   
• In addition, this c-di-AMP analog contains two phosphorothioate diester linkages, which prevent its degradation by the phosphodiesterases that are present in host cells or in the systemic circulation [4].
   
• Finally, this Rp, Rp dithio diastereoisomer was found to induce higher type I IFN production when compared to the Rp/Sp dithio diastereoisomers or c-di-AMP [3].

2’3’-c-di-AM(PS)₂ (Rp,Rp) VacciGrade™ is a high-quality pre-clinical grade.

Read our review on STING: Deciphering the STING Paradox

References:

1. Woodward JJ. et al., 2010. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science.328(5986):1703-5.
2. Jin L. et al., 2011. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di- GMP. J Immunol. 187(5):2595-601.
3. Corrales L et al., 2015. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11(7):1018-30.
4. Yan H. et al., 2008. Synthesis and immunostimulatory properties of the phosphorothioate analogs of cdiGMP. Bioorg. Med. Chem. Lett. 18, 5631–5634.