In vivo reprogramming of human telomerase reverse transcriptase (hTERT) by trans-splicing ribozyme to target tumor cells.
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.
Lee
Sang-Jin
SJ
Genitourinary Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.
Lee
Seong-Wook
SW
Jeong
Jin-Sook
JS
Kim
In-Hoo
IH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D065150:Cellular Reprogramming / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008967:Molecular Biology / Q000379:methods*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D016337:RNA, Catalytic / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology; D019098:Telomerase / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism; D020040:Trans-Splicing / Q000235:genetics*
D016337:RNA, Catalytic; D013937:Thymidine Kinase; C509186:TERT protein, human; D019098:Telomerase