Gene expression responses in vivo by human telomerase reverse transcriptase (hTERT)-targeting trans-splicing ribozyme
Experimental & Molecular Medicine
;
: 722-732, 2007.
Artículo
en Inglés
| WPRIM
| ID: wpr-21106
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
ARN Mensajero
/
ARN Neoplásico
/
Expresión Génica
/
Línea Celular
/
ARN Catalítico
/
Telomerasa
/
Trans-Empalme
/
Vectores Genéticos
/
Metástasis de la Neoplasia
/
Neoplasias
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2007
Tipo del documento:
Artículo
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