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KMID : 0545120120220030431
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 3 p.431 ~ p.435
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Cancer-Specific Induction of Adenoviral E1A Expression by Group I Intron-Based Trans-Splicing Ribozyme
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Won You-Sub
Lee Seong-Wook
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Abstract
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In this study, we describe a novel approach to achieve replicative selectivity of conditionally replicative adenovirus that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs. We developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce adenoviral E1A gene expression selectively in cancer cells that express the RNA. Western blot analysis showed that the ribozyme highly selectively triggered E1A expression in hTERT-expressing cancer cells. RT-PCR and sequencing analysis indicated that the ribozyme-mediated E1A induction was caused via a high fidelity trans-splicing reaction with the targeted residue in the hTERTexpressing cells. Moreover, reporter activity under the control of an E1A-dependent E3 promoter was highly transactivated in hTERT-expressing cancer cells. Therefore, adenovirus containing the hTERT RNA-targeting transsplicing ribozyme would be a promising anticancer agent through selective replication in cancer cells and thus specific destruction of the infected cells.
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KEYWORD
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Adenovirus, E1A, oncolytic virus, hTERT, RNA replacement, trans-splicing ribozyme
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