Virus‐Like Particle‐Induced cGAS‐STING Activation and AIM2 Inflammasome‐Mediated Pyroptosis for Robust Cancer Immunotherapy

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.