title: Use of tumor-targeting trans-splicing ribozyme for cancer treatment.
abstract: One of the major concerns with regard to successful cancer gene therapy is to enhance both efficacy and safety. Gene targeting may represent an attractive tool to combat cancer cells without damage to normal cells. Here, we introduce a tumor-targeting approach with the Tetrahymena group I intron-based trans-splicing ribozyme, which cleaves target RNA and trans-ligate an exon tagged at the end of the ribozyme onto the downstream U nucleotide of the cleaved target RNA. We develop a specific trans-splicing ribozyme that can target and reprogram human cytoskeleton-associate protein 2 (hCKAP2)-encoding RNA to trigger therapeutic transgene herpes simplex virus thymidine kinase (HSVtk) selectively in cancer cells that express the RNA. Adenoviral vectors encoding the hCKAP2-specific trans-splicing ribozyme are constructed for in vivo delivery into either subcutaneous tumor xenograft or orthotopically multifocal hepatocarcinoma. We present analyses of the efficacy of the recombinant adenoviral vectors in terms of cancer retardation, target RNA and cell specificity, and in vivo toxicity.
authors: Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin, South Korea.
authors: Seong-Wook
authors: SW
authors: Lee
authors: Jin-Sook
authors: JS
authors: Jeong
mesh_terms: D000256:Adenoviridae; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008967:Molecular Biology / Q000379:methods; D016337:RNA, Catalytic / Q000235:genetics* / Q000627:therapeutic use; D020040:Trans-Splicing / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C114988:CKAP2 protein, human; D003598:Cytoskeletal Proteins; D016337:RNA, Catalytic