Gene expression responses in vivo by human telomerase reverse transcriptase (hTERT)-targeting trans-splicing ribozyme.
- Author:
Min Sun SONG
1
;
Jin Sook JEONG
;
Kyung Sook CHO
;
Seong Wook LEE
Author Information
1. Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701, Korea. SWL0208@dankook.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
gene therapy;
microarray analysis;
RNA, catalytic;
TERT protein, human;
trans-splicing
- MeSH:
Animals;
Cell Line;
Gene Expression/*physiology;
Genetic Vectors;
Humans;
Mice;
Neoplasm Metastasis;
Neoplasms/genetics/pathology;
RNA, Catalytic/genetics/*metabolism;
RNA, Messenger/genetics/metabolism;
RNA, Neoplasm/genetics/metabolism;
Telomerase/antagonists & inhibitors/genetics/*metabolism;
Trans-Splicing/*genetics
- From:Experimental & Molecular Medicine
2007;39(6):722-732
- CountryRepublic of Korea
- Language:English
-
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.
