Anti-tumor analysis of the RIG-I agonist in vitro and in vivo.

Retinoic acid-inducible gene I (RIG-I), a key pattern recognition receptor (PRR) detecting cytosolic 5'-triphosphorylated double-stranded RNA (5'-ppp dsRNA), mediated antitumor immunity. Here, we evaluated RIG-I agonists as potential antitumor agents. To analyze the anti-tumor efficacy, we engineered a panel of 5'-PPP-modified stem-loop-structured RNAs leveraging the non-coding sequence of SARS-CoV-2. Through systematic screening, nCoV-L emerged as a potent RIG-I agonist that induced death in hepatocellular carcinomas (HCC), pulmonary carcinomas, and colorectal cancer (CRC) in vitro and suppressed tumor growth in vivo. Mechanistic studies demonstrated that nCoV-L elicited mitochondria-dependent apoptosis, supporting its potential as a broad-spectrum antitumor agent.