Exp Mol Med.
2007 Dec;39(6):722-732.
Gene expression responses in vivo by human telomerase reverse transcriptase (hTERT)-targeting trans-splicing ribozyme
- Affiliations
-
- 1Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701, Korea. SWL0208@dankook.ac.kr
- 2Department of Pathology, Medical Center for Cancer Molecular Therapy, Dong-A University College of Medicine, Busan 602-103, Korea.
- 3Research Institute and Hospital, National Cancer Center, Goyang 411-764, Korea.
Abstract
- A trans-splicing ribozyme which can specifically reprogram human telomerase reverse transcriptase (hTERT) RNA was previously suggested as a useful agent for tumor-targeted gene therapy. In this study, we evaluated in vivo function of the hTERT-targeting trans-splicing ribozymes by employing the molecular analysis of expression level of genes affected by the ribozyme delivery into peritoneal carcinomatosis mice model. To this effect, we constructed adenoviral vector encoding the specific ribozyme. Noticeably, more than four-fold reduction in the level of hTERT RNA was observed in tumor nodules by the systemic infection of the ribozyme-encoding virus. Such hTERT RNA knockdown in vivo induced changes in the global gene expression profile, including the suppression of specific genes associated with anti-apoptosis including bcl2, and genes for angiogenesis and metastasis. In addition, specific trans-splicing reaction with the targeted hTERT RNA took place in the tumors established as peritoneal carcinomatosis in mice by systemic delivery of the ribozyme. In conclusion, this study demonstrates that an hTERT-specific RNA replacement approach using trans-splicing ribozyme represents a potential modality to treat cancer.
MeSH Terms
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Specificity of Intracellular Trans-Splicing Reaction by hTERT-Targeting Group I Intron
- An RNA Mapping Strategy to Identify Ribozyme-Accessible Sites on the Catalytic Subunit of Mouse Telomerase
- In Vivo Target RNA Specificity of Trans-Splicing Phenomena by the Group I Intron
- The Expression of Telomerase Reverse Transcriptase Protein is an Independent Prognostic Marker in Early Stage Non-Small Cell Lung Carcinomas
- Change of the Expression of Human Telomerase Reverse Transcriptase mRNA and Human Telomerase RNA after Cisplatin and 5-Fluorouracil Exposure in Head and Neck Squamous Cell Carcinoma Cell Lines
