Tumor-specific gene delivery using RNA-targeting Tetrahymena group I intron

Abstract

Current gene therapy protocols against cancer often have limited target specificity. Here, a novel tumor-specific targeted gene delivery procedure, which is based on Tetrahymena group I intron ribozyme, is presented. This ribozyme can target a cancer-specific transcript and then replace the RNA with new transcripts, resulting in induction of the transgene activity selectively in cancer cells that express the target RNA. The RNA replacement occurs by trans-splicing reaction with high fidelity with the target RNA. In addition, the ribozyme can specifically inhibit function of the targeted gene in the cells expressing the RNA. Moreover, the ribozyme can selectively deliver cytotoxin gene activity into cancer cells expressing the RNA and thereby specifically hampers the survival of these cells. These findings suggest that the trans-splicing ribozyme that targets the cancer-specific RNA could be a potential agent for specific tumor gene therapy.