title: In vivo reprogramming of human telomerase reverse transcriptase (hTERT) by trans-splicing ribozyme to target tumor cells.
abstract: 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.
authors.affiliation: Genitourinary Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Lee
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Jeong
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
mesh_terms: 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*
chemical_list: D016337:RNA, Catalytic; D013937:Thymidine Kinase; C509186:TERT protein, human; D019098:Telomerase