Affiliation:
1. State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Chemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Nanjing 210023 China
2. Molecular Science and Biomedicine Laboratory (MBL) State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Aptamer Engineering Center of Hunan Province Hunan University Changsha Hunan 410082 China
3. Zhejiang Cancer Hospital Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China
Abstract
AbstractcGAS‐STING‐mediated DNA sensing is demonstrated to be critical for launching antitumor immunity. However, DNA‐based cGAS‐STING agonists are rarely reported owing to low cell permeability, poor biostability and, especially, limited length of exogenous DNA. Here, we present a virus‐like particle which is self‐assembled from long DNA building blocks generated through rolling‐circle amplification (RCA) and covered with cationic liposomes. Based on long and densely packed DNA structure, it could efficiently induce liquid phase condensation of cGAS and activate STING signaling to produce inflammatory cytokines. Moreover, this virus‐like particle could also trigger the formation of AIM2 inflammasome to induce gasdermin D‐mediated pyroptosis, boosting antitumor immunity. Thus, this study provides a simple and robust strategy for cancer immunotherapy for clinical application. This is the first study to report the intrinsic immunogenicity of RCA products, thus facilitating their biomedical applications.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Cited by
2 articles.
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