biostudies-literatureWang YNIBIB NIH HHSNIAID NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | National Institutes of Health856-866https://www.ebi.ac.uk/biostudies/studies/S-EPMC11948844biostudies-literatureUnknown19(6)The efficacy of STING (stimulator of interferon genes) agonists is due to various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours, and a complex balance between tumour control and progression. Here we report a universal STING mimic (uniSTING) based on a polymeric architecture. UniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNPs) results in potent antitumour efficacy across established and advanced metastatic tumour models, including triple-negative breast cancer, lung canceNature nanotechnologyUniversal STING mimic boosts antitumour immunity via preferential activation of tumour control signalling pathways.PMC11948844R01 EB032865R01EB032865R35 CA232109R01-AI029564R01 AI029564T32 CA196589R35-CA232109McCabe EYang YLi SHu MWithrow AMLiu RZhang LWang YTing JPfalseUniversal STING mimic boosts antitumour immunity via preferential activation of tumour control signalling pathways.The efficacy of STING (stimulator of interferon genes) agonists is due to various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours, and a complex balance between tumour control and progression. Here we report a universal STING mimic (uniSTING) based on a polymeric architecture. UniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNPs) results in potent antitumour efficacy across established and advanced metastatic tumour models, including triple-negative breast cancer, lung cance2024-01-01T00:00:00Z2024 Jun2025-06-28T03:05:23.86Z2025-06-28T03:05:23.86ZS-EPMC119488443848083610.1038/s41565-024-01624-2