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Re-Engineering of Carcinoembryonic Antigen RNA with the Group I Intron of Tetrahymena thermophila by Targeted Trans-Splicing

JUNG HEUNG-SU (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)
LEE SEONG-WOOK (Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University)

Publication Information

Journal of Microbiology and Biotechnology / v.15, no.6, 2005 , pp. 1408-1413 More about this Journal

Abstract

Elevated expression of carcinoembryonic antigen (CEA) has been implicated in various biological aspects of neoplasia such as tumor cell adhesion, metastasis, blocking of cellular immune mechanisms, and antiapoptosis function. Thus, the CEA could be an important target for anticancer therapy. In this study, we developed Tetrahymena group 1 intron-based trans-splicing ribozymes that can specifically target and replace CEA RNA. To this end, we first determined which regions of the CEA RNA were accessible to ribozymes by employing an RNA mapping strategy that was based on a trans-splicing ribozyme library. Next, we assessed the ribozyme activities by comparing the trans-splicing activities of several ribozymes that targeted different regions of the CEA RNA, and then the ribozyme that could target the most accessible site was observed to be the most active with high fidelity in vitro. Moreover, the specific trans-splicing ribozyme was found to react with and altered the target CEA transcripts in mammalian cells with high fidelity. These results suggest that the Tetrahymena ribozyme can be utilized to replace CEA RNAs in tumors with a new RNA-harboring anticancer activity, thereby hopefully reverting the malignant phenotype.

Keywords

Carcinoembryonic antigen; group I intron; RNA replacement; Tetrahymena thermophila; trans-splicing ribozyme;

Citations & Related Records

Times Cited By Web Of Science : 2 (Related Records In Web of Science)

Reference

1	Benchimol, S., A. Fuks, S. Jothy, N. Beauchemin, K. Shirota, and C. P. Stanners. 1989. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57: 327-334 DOI ScienceOn
2	Bjerner, J., Y. Lebedin, L. Bellanger, M. Kuroki, J. E. Shively, T. Varaas, K. Nustad, S. Hammarstrom, and O. P. Bormer. 2002. Protein epitopes in carcinoembryonic antigen. Tumor Biol. 23: 249-262 DOI ScienceOn
3	Goldenberg, D. M., R. M. Sharkey, and F. J. Primus. 1976. Carcinoembryonic antigen in histopathology: Immunoperoxidase staining of conventional tissue sections. J. Natl. Cancer Inst. 57: 11-22 DOI
4	Hammarstrom, S., A. Olsen, S. Teglund, and V. Baranov. 1998. The nature and expression of the human CEA family, pp 1-30. In C. P. Stanners (ed.), Cell Adhesion and Communications Mediated by the CEA Family: Basic and Clinical Perspectives, vol. 5. Harwood Academic, Amsterdam
5	Jessup, J. M. and P. Thomas. 1998. CEA and metastasis: A facilitator of site-specific metastasis, pp 195-222. In: C. P. Stanners (ed.). Cell Adhesion and Communication by the CEA Family, vol 5. Harwood Academic, Amsterdam
6	Jones, J. T., S.-W. Lee, and B. A. Sullenger. 1996. Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells. Nat. Med. 2: 643-648 DOI ScienceOn
7	Kim, H., S.-J. Kim, S.-N. Park, and J.-W. Oh. 2004. Antiviral effect of amphotericin B on Japanese encephalitis virus replication. J. Microbiol. Biotechnol. 14: 121-127
8	Lee, J. H., S. W. Nam, and Y. T. Kim. 2003. Isolation of cDNAs for gonadotropin-II of flounder (Paralichthys olivaceus) and its expressions in adult tissues. J. Microbiol. Biotechnol. 13: 710-716
9	Watanabe, T. and B. A. Sullenger. 2000. Induction of wildtype p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts. Proc. Natl. Acad. Sci. USA 97: 8490-8494
10	Hashino, J., Y. Fukuda, S. Oikawa, H. Nakazato, and T. Nakanishi. 1994. Metastatic potential of human colorectal carcinoma SW1222 cells transfected with cDNA encoding carcinoembryonic antigen. Clin. Exp. Metastasis 12: 324-328 DOI ScienceOn
11	Jaeger, J., D. Turner, and M. Zuker. 1989. Improved predictions of secondary structures for RNA. Proc. Natl. Acad. Sci. USA 86: 7706-7710
12	Gold, P. and N. A. Goldenberg. 1997. The carcinoembryonic antigen (CEA): Past, present, and future. McGill J. Med. 3: 46-66
13	Lan, N., R. P. Howrey, S.-W. Lee, C. A. Smith, and B. A. Sullenger. 1998. Ribozyme-mediated repair of sickle $\beta$ -globin mRNAs in erythrocyte precursors. Science 280: 1593-1596 DOI PUBMED ScienceOn
14	Oikawa, S., C. Inuzuka, M. Kuroki, Y. Matsuoka, G. Kosaki, and H. Nakazato. 1989. Cell adhesion activity of non-specific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: Homophilic and heterophilic adhesion. Biochem. Biophys. Res. Commun. 164: 39-45 DOI ScienceOn
15	Shin, K.-S., B. A. Sullenger, and S.-W. Lee. 2004. Ribozyme-mediated induction of apoptosis in human cancer cells by targeted repair of mutant p53 RNA. Mol. Ther. 10:365-372 DOI ScienceOn
16	Byun, J., N. Lan, M. Long, and B. A. Sullenger. 2003. Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes. RNA 9: 1254-1263 DOI ScienceOn
17	Lee, H. J. and M. B. Gu. 2003. Effect of benzo[a]pyrene on genes related to the cell cycle and cytochrome P450 of Saccharomyces cerevisiae. J. Microbiol. Biotechnol. 13: 624-627
18	Shively, J. E. and J. D. Beatty. 1985. CEA-related antigens: Molecular biology and clinical significance. Crit. Rev. Oncol. Hematol. 2: 355-399 DOI ScienceOn
19	Sullenger, B. A. and T. R. Cech. 1994. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature 317: 619-622
20	Ryu, K.-J., J.-H. Kim, and S.-W. Lee. 2003. Ribozymemediated selective induction of new gene activity in hepatitis C virus internal ribosome entry site-expressing cells by targeted trans-splicing. Mol. Ther. 7: 386-395 DOI ScienceOn
21	Blumenthal, R. D., R. M. Sharkey, L. Haywood, A. M. Natale, G. Y. Wong, J. A. Siegel, S. J. Kennel, and D. M. Goldenberg. 1992. Targeted therapy of athymic mice bearing GW-39 human colonic cancer micrometastases with $^{131}I$ -labeled monoclonal antibodies. Cancer Res. 52: 6036-6044
22	Phylactou, L. A., C. Darrah, and M. A. J. Wood. 1998. Ribozyme mediated trans-splicing of a trinucleotide repeat. Nat. Genet. 18: 378-381 DOI ScienceOn
23	Eidelman, F. J., A. Fuks, L. DeMarte, M. Taheri, and C. P. Stanners. 1993. Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts. J. Cell Biol. 123: 467-475 DOI ScienceOn
24	Hammarstrom, S. 1999. The carcinoembryonic antigen (CEA) family: Structures, suggested functions and expression in normal and malignant tissues. Semin. Cancer Biol. 9: 67-81 DOI PUBMED ScienceOn
25	Sullenger, B. A. and E. Gilboa. 2002. Emerging clinical applications of RNA. Nature 418: 252-258 DOI ScienceOn
26	Sullenger, B. A. and T. R. Cech. 1995. RNA repair: A new possibility for gene therapy. J. NIH Res. 7: 46-47
27	Screaton, R. A., L. Z. Penn, and C. P. Stanners. 1997. Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation. J. Cell. Biol. 137: 939-952 DOI ScienceOn
28	Rogers, C. S., C. G. Vanoye, B. A. Sullenger, and A. L. George, Jr. 2002. Functional repair of a mutant chloride channel using a trans-splicing ribozyme. J. Clin. Invest. 110: 1783-1798 DOI
29	Lan, N., B. L. Rooney, S.-W. Lee, R. P. Howrey, C. A. Smith, and B. A. Sullenger. 2000. Enhancing RNA repair efficiency by combining trans-splicing ribozymes that recognize different accessible sites on a target RNA. Mol. Ther. 2: 245-255 DOI ScienceOn
30	Stanners, C. P. and A. Fuks. 1998. Properties of adhesion mediated by the human CEA family, pp 57-72. In: C. P. Stanners (ed.), Cell Adhesion and Communication by the CEA Family, vol 5. Harwood Academic, Amsterdam
31	Kim, S., J. S. Kang, D. D. Jang, K. Lee, S. A. Kim, B. S. Han, and Y. I. Park. 2004. Differential gene expression in estradiol-3-benzoate-treated liver and chemically-induced hepatocellular carcinoma. J. Microbiol. Biotechnol. 14: 1286-1294