Specific Regression of Human Cancer Cells by Ribozyme-Mediated Targeted Replacement of Tumor-Specific Transcript

摘要: In this study, we describe a novel approach to human cancer therapy that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs with new transcripts exert therapeutic activities. We have developed specific ribozyme can reprogram telomerase reverse transcriptase (hTERT) RNA induce transgene activity selectively in cells express the RNA. The triggering expression was accomplished via high-fidelity reaction targeted residue hTERT-expressing cells. also induced cytotoxic various cells, hence retarding growth those Efficient and cell regression detected ganciclovir (GCV) treatment only hTERT-positive which were established stably contains herpes simplex virus thymidine kinase (HSV-tk) gene. Tissue-specific could further augment target specificity ribozyme. Importantly, observed efficient tumors GCV mice had been inoculated subcutaneously expressed HSV-tk. These results suggest hTERT RNA-targeting be powerful agent for tumor-targeted gene therapy.