cGAMP (cyclic-GMP-AMP) functions as an endogenous second messenger that triggers interferon production in response to cytosolic DNA. It is a STING ligand which binds to STING, leading to the activation of IRF3 and induction of interferon-β[4]. cGAS-synthesized cGAMP is transferred from producing cells to neighbouring cells through gap junctions, where it promotes STING activation and thus antiviral immunity independently of type I IFN signaling, identifying cGAS-triggered cGAMP transfer as a novel host strategy that serves to rapidly convey antiviral immunity in a transcription-independent, horizontal manner[5]. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1[6].
cGAMP 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
1 μM
1 h
To evaluate the effect of cGAMP on phosphorylation of STING, TBK1, and IRF3
Nature. 2022 Apr;604(7906):557-562
mouse splenic B cells
5μg/mL
24 h
To investigate the effect of cGAMP on IL-35 and IL-10 expression in B cells, results showed that cGAMP significantly increased the frequency of IL-35 and IL-10 in WT but not in Tmem173−/− B cells.
Nature. 2022 Oct;610(7931):373-380
THP-1 cells
100 μM
24 h
Evaluate the role of P2RX7 in cGAMP-induced STING activation
J Neuroinflammation. 2025 Mar 1;22(1):58
Primary human macrophages
100 μM
24 h
Evaluate the role of P2RX7 in cGAMP-induced STING activation
J Neuroinflammation. 2025 Mar 1;22(1):58
Bone marrow-derived dendritic cells (BMDCs)
1 μg/mL
24 and 48 h
To evaluate the ability of cGAMP as a STING agonist to induce IFN-β secretion in BMDCs. Results showed that cGAMP encapsulated in Ace-DEX MPs induced higher IFN-β secretion compared to soluble or lipofectamine-complexed cGAMP.
Int J Pharm. 2022 Jun 25;622:121839
bone marrow-derived macrophage (BMDMs)
100 nM
4 h
To evaluate the activation of STING pathway and type I IFN production by NP-cGAMP. NP-cGAMP induced a drastic increase in expression of Ifnb1 and Ifna1, as well as other proinflammatory genes.
Nat Commun. 2019 Nov 8;10(1):5108
bone marrow-derived dendritic cells (BMDCs)
100 nM
4 h
To evaluate the activation of STING pathway and type I IFN production by NP-cGAMP. NP-cGAMP induced a drastic increase in expression of Ifnb1 and Ifna1, as well as other proinflammatory genes.
Nat Commun. 2019 Nov 8;10(1):5108
alveolar macrophage (AM)
100 nM
4 h
To evaluate the activation of STING pathway and type I IFN production by NP-cGAMP. NP-cGAMP induced a drastic increase in expression of Ifnb1 and Ifna1, as well as other proinflammatory genes.
Nat Commun. 2019 Nov 8;10(1):5108
cGAMP 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Immunization model
Footpad injection
5 μg,20 μL
Single or multiple immunizations
CGAMP enhances the differentiation of germinal center B cells (BGC) and plasma cells (BPC), and increases antigen-specific antibody production.
Front Immunol. 2024 Apr 12;15:1340001
DBA/2 J mice
Influenza viral challenge model
Intramuscular injection
1 µg/mouse
Vaccinated at weeks 0, 3, and 6, totaling 3 doses
Evaluated the protective immune responses of cGAMP MPs adjuvanted COBRA HA vaccines in mice, showing mitigation of disease symptoms and reduced pulmonary viral titers
mSphere. 2024 Jul 30;9(7):e0016024
Mice
STING mutant mice (S365A, L373A, ΔCTT)
Intratumoral injection
10 μg
Administered on days 5, 8, 11, and 14 after tumor implantation
To study the antitumor effect of cGAMP in STING mutant mice. Results showed that STING-S365A mice retained the antitumor response, while L373A and ΔCTT mice lost this effect.
Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2100225118
Mice
Implanted LLC tumor model, MMTV-PyMT spontaneous breast cancer model
Intratumoral injection
14 μg, 70 μl
Single injection, sampled 24 hours later
Evaluate the effect of cGAMP on tumor vascular disruption and anti-tumor growth, results showed cGAMP significantly induced tumor endothelial cell apoptosis and suppressed tumor growth
Nat Commun. 2021 Jul 20;12(1):4405
C57BL/6J mice
Influenza vaccine immunization model
Intramuscular injection
1 μg
According to the immunization schedule in Figure 4A
To evaluate the immunogenicity of cGAMP as an adjuvant in COBRA HA vaccine. Results showed that cGAMP MP-adjuvanted groups induced higher anti-Y2 IgG antibody titers than the unadjuvanted group, and compared to Addavax, cGAMP MPs induced a stronger Th1-skewed immune response (IgG2C).
Int J Pharm. 2022 Jun 25;622:121839
Mice
Pancreatic ductal adenocarcinoma (PDAC) model
Intravenous injection
10μg/mL
Every three days for a total of 4 times
To evaluate the effect of cGAMP on tumor growth and immune cell infiltration, results showed that cGAMP increased the percent of CD19+ B cells among the CD45+ cells and the absolute number of B cells in the tumours by day 21 but had no effect on tumour growth.
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