Our understanding of RNA has evolved over the last 20 years from the initial concept that RNA is simply an intermediate in protein synthesis or a structural component maintaining and expressing genetic information. Subsequently, the non-coding RNAs have attracted huge interest and have been developed as therapeutic reagents as well as research tools. An example of RNA-based therapeutic application is the Tetrahymena group I intron-based trans-splicing ribozyme, which cleaves target RNA and trans-ligates an exon tagged at its 3' end onto the downstream U nucleotide of the targeted RNA. Here, we describe the specific trans-splicing ribozyme that can sense and reprogram human telomerase reverse transcriptase (hTERT)-encoding RNA. This ribozyme converts hTERT RNA to therapeutic transgene herpes simplex virus (HSV) thymidine kinase (tk) and exhibits cytotoxicity to various hTERT-expressing cancer cells. For use in cancer therapy, CMV promoter-driven hTERTRibozyme.HSVtk expression cassette is inserted into adenovirus genome and delivered into either subcutaneous or intraspleenic liver-metastasized xenograft. We present here an evaluation of the inhibitory effects of CMV.hTERTRibozyme.HSVtk on tumor growth.
CITATION STYLE
Lee, S. J., Lee, S. W., Jeong, J. S., & Kim, I. H. (2010). In vivo reprogramming of human telomerase reverse transcriptase (hTERT) by trans-splicing ribozyme to target tumor cells. Methods in Molecular Biology (Clifton, N.J.), 629, 307–321. https://doi.org/10.1007/978-1-60761-657-3_20
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