1887

Abstract

The effect of a series of antisense oligodeoxyribonucleotides [oligo(dN)] on the expression of the surface antigen (HBsAg) gene of human hepatitis B virus (HBV) was examined using hepatocellular carcinoma cells that contain integrated HBV genomes. Of a number of antisense oligo(dN)s tested, synthetic 15-mers directed at the cap site of mRNA and regions of the translational initiation site of the HBsAg gene were found to be highly effective and inhibited viral gene expression by as much as 96 %. The inhibition was specific to the HBsAg gene and appeared to be at the level of translation. These results suggest a therapeutic potential for antisense oligo(dN) in the treatment of patients who are chronically infected with HBV.

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1990-12-01
2024-12-14
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References

  1. Alexander J., Bey E., Whitcutt M., Gear J. 1976; Adaptation of cells derived from human malignant tumours to growth in vitro . South African Journal of Medical Sciences 41:89–95
    [Google Scholar]
  2. Beasley R. P., Lin C. C., Hwang J.-Y., Chen C. S. 1981; Hepatocellular carcinoma and hepatitis B virus, a progressive study of 22707 men in Taiwan. Lancet ii:1129–1133
    [Google Scholar]
  3. Chisari F. V., Klopchin K., Moriyama T., Pasquinelli C., Dunsford H. A., Sell S., Pinkert C. A., Brinster R. L., Palmiter R. D. 1989; Molecular pathogenesis of hepatocellular carcinoma in HBV transgenic mice. Cell 59:1145–1156
    [Google Scholar]
  4. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162:156–159
    [Google Scholar]
  5. Eckstein F. 1985; Nucleoside phosphorothioates. Annual Review of Biochemistry 54:367–402
    [Google Scholar]
  6. Ganem D. 1982; Persistent infection of humans with hepatitis B virus: mechanisms and consequences. Review of Infectious Diseases 4:1026–1047
    [Google Scholar]
  7. Goodchild J., Agrawal S., Civeira M. P., Sarin P., Sun D., Zamecnik P. C. 1988; Inhibition of human immunodeficiency virus replication by antisense oligodeoxynucleotides. Proceedings of the National Academy of Sciences, U.S.A 85:5507–5511
    [Google Scholar]
  8. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kodes L. 1983 Molecular and Cellular Biology 3:787–795
    [Google Scholar]
  9. Hollinger F. B., Melnick J. L., Robinson W. S. 1985 Viral Hepatitis New York: Raven Press;
    [Google Scholar]
  10. Knowles B. B., Howe C. C., Aden D. P. 1980; Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209:497–499
    [Google Scholar]
  11. Macnab G. M., Alexander J. J., Lecatsas G., Bey E. M., Urbanowicz J. M. 1976; Hepatitis B surface antigen produced by a human hepatoma cell line. British Journal of Cancer 34:509–515
    [Google Scholar]
  12. Matsukura M., Zon G., Shinozuka K., Stein C. A., Mitsuya H., Cohen J. S., Broder S. 1988; Synthesis of phosphorothioate analogues of oligodeoxyribonucleotides and their antiviral activity against human immunodeficiency virus. Gene 64:343–347
    [Google Scholar]
  13. Maupas P., Melnick J. L. 1981; Hepatitis B infection and primary liver cancer. Progress in Medical Virology 27:1–5
    [Google Scholar]
  14. Moriarty A. M., Hoyer B. H., Shih J. W., Gerin J. L., Hamer H. 1981; Expression of the HBV surface antigen gene in cell culture by using a simian virus 40 vector. Proceedings of the National Academy of Sciences, U.S.A 78:2606–2610
    [Google Scholar]
  15. Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. 1983; The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw. Nucleic Acids Research 11:1747–1757
    [Google Scholar]
  16. Quinn T. C., Piot P., Mccormick J. B., Feinsod F. M., Taelman H., Kapita B., Faaci A. S. 1987; Serologic and immunologic studies in patients with AIDS in North America and Africa. Journal of the American Medical Association 257:2617–2621
    [Google Scholar]
  17. Rivkina M. B., Lunin V. G., Mahov A. M., Tikchonenko T. I., Kukain R. A. 1988; Nucleotide sequence of integrated hepatitis B virus DNA and human flanking regions in the genome of the PLC/PRF/5 cell line. Gene 64:285–296
    [Google Scholar]
  18. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  19. Seto E., Benedict T. S., Peterlin M., Ou J.-H. 1988; Transactivation of the human immunodeficiency virus long terminal repeat by the hepatitis B virus X protein. Proceedings of the National Academy of Sciences, U.S.A 85:8286–8290
    [Google Scholar]
  20. Stein A., Cohen J.-S. 1988; Oligodeoxynucleotides as inhibitors of gene expression. Cancer Research 48:2659–2668
    [Google Scholar]
  21. Szmuness W. 1988; Recent advances in the study of the epidemiology of hepatitis B. American Journal of Pathology 81:629–649
    [Google Scholar]
  22. Tiollais P., Pourcel C., Dejean A. 1985; The hepatitis B virus. Nature; London: 317489–495
    [Google Scholar]
  23. Twu J.-S., Robinson W. S. 1989; Hepatitis B virus X gene can trans-activate heterologous viral sequences. Proceedings of the National Academy of Sciences, U.S.A 86:2046–2050
    [Google Scholar]
  24. Walder R. Y., Walder J. A. 1988; Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proceedings of the National Academy of Sciences, U.S.A 85:5011–5015
    [Google Scholar]
  25. Zamecnik P. C., Goodchild J., Taguchi Y., Sarin P. 1986; Inhibition of replication and expression of human T-cell lympho- tropic oligonucleotides complementary to viral RNA. Proceedings of the National Academy of Sciences, U.S.A 83:4143–4146
    [Google Scholar]
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