A virus-inspired RNA mimicry approach for effective cancer immunotherapy

Abstract

Current cancer treatments, including chemotherapy, surgery, and radiation, often present significant challenges such as severe side effects, drug resistance, and damage to healthy tissues. To address these issues, we introduce a virus-inspired RNA mimicry approach, specifically through the development of uridine-rich nanoparticles (UNPs) synthesized using the rolling circle transcription (RCT) technique. These UNPs are designed to mimic the poly-U tail sequences of viral RNA, effectively engaging RIG-I-like receptors (RLRs) such as MDA5 and LGP2 in cancer cells. Activation of these receptors leads to the upregulation of pro-inflammatory cytokines and the initiation of apoptosis, resulting in targeted cancer cell death. Importantly, this strategy overcomes the limitations of traditional therapies and enhances the effectiveness of existing RIG-I stimulators, such as poly(I:C), which has often exhibited toxicity in clinical settings due to delivery methods. Our in vivo studies further demonstrate the ability of UNPs to significantly reduce tumor growth without adverse effects, highlighting their potential as a novel and effective approach in cancer immunotherapy. This approach offers new therapeutic strategies that leverage the body's innate antiviral mechanisms for cancer treatment.