Advertisement

Comparative Pharmacokinetics of Antisense Oligonucleotides

  • Sudhir Agrawal
  • Jamal Temsamani
Part of the Methods in Molecular Medicine book series (MIMM, volume 1)

Abstract

Antisense oligonucleotides have attracted special interest as a novel class of therapeutic agents for the treatment of viral infection, cancers, and genetic disorders because of their ablhty to inhibit expression of a disease-associated gene in a sequence-specific manner. Gene expression is inhibited by hybrid ization of the oligonucleotide to sequences in the gene or the messenger RNA (mRNA) target by Watson-Crick base pairing. The first example of specific mhibition of gene expression by an ohgonucleotide was reported by Zamecnik and Stephenson (1), who demonstrated that a short oligonucleotide inhibited Rous sarcoma virus replication in cell culture. Since then, the field has progressed enormously. Numerous studies have demonstrated the ability of antisense oligonucleotides to modulate gene expression (2, 3, 4). Accompanying chapters in this volume describe the use of antisense oligonucleotides for vanous disease targets.

Keywords

Antisense Oligonucleotide Fecal Excretion Degrade Product Minor Pathway Hybrid Oligonucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Zamecnik, P C. and Stephenson, M. L (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligonucleotide. Proc. Natl. Acad. Sci USA 75, 280–284.PubMedCrossRefGoogle Scholar
  2. 2.
    Agrawal, S (1992) Antisense oligonucleotides as antiviral agents. TIBTECH 10, 152–157Google Scholar
  3. 3.
    Stein, C. A. and Cheng, Y. C. (1993) Antisense oligonucleotides as therapeutic agents-is the bullet really magical? Science 261, 1004–1012PubMedCrossRefGoogle Scholar
  4. 4.
    Temsamani, J. and Agrawal, S. (1995) Antisense oligonucleotides as antiviral agents, in Advances in Antiviral Drug Design, vol. 2 (de Clercq, E, ed.), JAI, in pressGoogle Scholar
  5. 5.
    Uhlmann, E and Peyman, A (1990) Antisense oligonucleotides A newtherapeutic principle Chem Rev. 90, 543–584.CrossRefGoogle Scholar
  6. 6.
    Inagaki, M, Togawa, K., Carr, B I, Ghosh, K., and Cohen, J S. (1992) Antisense oligonucleotides: inhibition of liver cell proliferation and in viva disposition Transplant Proc 26, 2971, 2972.Google Scholar
  7. 7.
    Zendegui, J., Vasquez, K., Tinsley, J., Kessler, D. J., and Hogan, M. E (1992) Invivo stability and kinetics of absorption and disposition of 3′ phosphopropyl amine oligonucleotides Nucleic Acids Res 20, 307–314PubMedCrossRefGoogle Scholar
  8. 8.
    Sands, H., Gorey-Feret, L J., and Cocuzza, A. J. (1994) Biodistrtbution and metabolism of internally3H-labeled oligonucleotides I Comparison of a phosphodiester and a phosphorothioate. Mol Pharmacol 45, 932–943PubMedGoogle Scholar
  9. 9.
    Agrawal, S., Temsamani, J, Galbraith, W, and Tang, J.-Y. (1995) Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet 28, 7–16PubMedCrossRefGoogle Scholar
  10. 10.
    Agrawal, S., ed (1993) Protocols for Oligonucleotides and Analogs Synthesis and Properties Humana, Totowa, NJ.Google Scholar
  11. 11.
    Agrawal, S. and Lisziewicz, J (1994) Potential for HIV-l treatment with antisense oligonucleotides J Biotechnol Health Care 1, 167–182Google Scholar
  12. 12.
    Lisziewicz, J, Sun, D, Welchold, F.F, Thierry, A., Lusso, P., Tang, J. Y., Gallo, R.C, and Agrawal, S (1994) Antisense oligodeoxynucleotide phosphorothioate complementary to gag mRNA blocks replication of human immunodeticiency virus type 1 in human peripheral blood cells. Proc Natl Acad Sci USA 91, 7942–7946PubMedCrossRefGoogle Scholar
  13. 13.
    Cohen, J S (1993) Phosphorothioate oligonucleotides, in Antisense Research and Applications (Crooke, S T. and Lebleu, B., eds.), CRC, Boca Raton, FL, pp. 205–222Google Scholar
  14. 14.
    Stem, C.A. and Cohen, J S (1989) Phopshorothioate oligodeoxynucleotide analogs, in Oligodeoxynucleotides’ Antisense inhibitors of Gene Expression (Cohen, J S., ed.), CRC, Boca Raton, FL, pp 97–120.Google Scholar
  15. 15.
    Akhtar, S and Juliano, R. L (1992) Cellular uptake and intracellular fate of antisense oligonucleotides Trends Cell Biol. 2, 139–144PubMedCrossRefGoogle Scholar
  16. 16.
    Temsamani, J., Kubert, M., Tang, J.-Y., Padmapriya, A. A., and Agrawal, S (1994) Cellular uptake of oligodeoxynucleotide phosphorothioates and their analogs Antisense Res Dev 4, 35–542.PubMedGoogle Scholar
  17. 17.
    Agrawal S (1991) Antisense oligonucleotides: a possible approach for chemotherapy of AIDS, in Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS (Wickstrom, E., ed.), Wiley-Liss, New York, pp 143–158Google Scholar
  18. 18.
    Agrawal, S, Temsamani, J., and Tang, J.-Y. (1991) Pharmacokinetics bio-distribution, and stability of oligodeoxynucleotide phosphorothioates in mice Proc Natl Acad SCI USA 88, 7595–7599.PubMedCrossRefGoogle Scholar
  19. 19.
    Temsamani, J, Tang, J.-Y, Padmapriya, A A., Kubert, M., and Agrawal, S. (1993) Pharmacokinetics, biodistribution and stability of capped oligodeoxy-nucleotide phosphorothioates in mice. Antisense Res Dev 3, 277–284PubMedGoogle Scholar
  20. 20.
    Temsamani, J, Tang, J-Y., and Agrawal, S (1992) Capped oligodeoxynucleotide phosphorothioates. pharmacokinetics and stability in mice. Ann NY Acad Sci. 660, 318–320PubMedCrossRefGoogle Scholar
  21. 21.
    Iversen, P L, Mata, J, Tracewell, W.G., and Zon, G. (1994) Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in adult male rat following single injections andcontinuous infusion. Antisense Res. Dev 4, 43–52PubMedGoogle Scholar
  22. 22.
    Cossum, P A, Sasmor, H, Dellinger, D, Truong, L., Cummins, L, Owens, S.R, Markham, P.M, Shea, J.P., and Crooke, S (1993) Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats J Pharmacol Exp Ther USA 267, 1181–1190Google Scholar
  23. 23.
    Agrawal, S., Mayrand, S M., Zamecnik, P.C, and Pederson, T (1990) Site specific excision from RNA by RNase H and mixed phosphate backbone oligodeoxynucleotides. Proc Natl Acad Sci USA 87, 1401–1405.PubMedCrossRefGoogle Scholar
  24. 24.
    Miller, P S., Ts′o, POP, Hogrefe, R I, Reynolds, M A., and Arnold, L J (1993) J Anticode oligonucleoside methylphosphonates and then Psoralen derivatives, in Antisense Research and Applications (Crooke, S T and Lebleu, B., eds), CRC, Boca Raton, FL, pp 189–204Google Scholar
  25. 25.
    Chem, T L., Miller, P., Ts’o, P., and Colvin, O. M. (1990) Disposition and metabolism of oligodeoxynucleoside methylphosphonate following a single ivinjection in mice Drug Metab Dispos 18, 815–818PubMedGoogle Scholar
  26. 26.
    Metelev, V, Lisziewicz, J., and Agrawal, S. (1994) Study of antisense oligonucle-otide phosphorothioates containing segments of oligodeoxynucleotides and 2′-O-methyloligoribonucleotides Bioorg Med Chem Lett 4, 2929–2934CrossRefGoogle Scholar
  27. 27.
    Tang, J.Y., Temsamani, J, and Agrawal, S (1993) Self-stabilized antisense oligonucleotide phosphorothioates’ properties and anti-HIV activity. Nucleic Acids Res 21, 2729–2735PubMedCrossRefGoogle Scholar
  28. 28.
    Beaucage, S L (1993) Oligodeoxyribonucleotide synthesis-phosphorothioate approach, in Protocols for Oligonucleotides and Analogs (Agrawal, S., ed), Humana, Totowa, NJ, pp 33–61CrossRefGoogle Scholar
  29. 29.
    Froehler, B. C (1993) Oligodeoxyribonucleotide synthesis-H phosphonate approach, in Protocols for Oligonucleotides and Analogs (Agrawal, S., ed.), Humana, Totowa, NJ, pp. 63–80CrossRefGoogle Scholar
  30. 30.
    Zhang, R, Diasio, R B., Lu, Z., Liu, T., Jiang, Z., Galbraith, W.M., and Agrawal, S. (1995) Pharmacokinetics and tissue distribution in rats of anoligodeoxynucleotide phosphorothioate (GEM 91) developed as a therapeutic agent for human immunodeficiency virus type-l. Biochem Pharmacol 49, 929–939PubMedCrossRefGoogle Scholar
  31. 31.
    Zhang, R, Lu, Z., Zhang, H., Dtasio, R. B, Habus, I, Jiang, Z., Iyer, R P., Yu, D., and Agrawal, S (1995) In Vivo stability and metabolism of a “hybrid” oligonucleoside phosphorothioate in rats Biochem Pharmacol 50, 545–556PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang, R, Lu, Z., Zhang, X., Diasio, R., Liu, T., Jiang, Z., and Agrawal, S (1995) In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothuioate in rats Clin Chem 41, 836–843PubMedGoogle Scholar
  33. 33.
    Zhang, R., Iyer, R P., Weitan, T., Yu, D., Zhang, X, Lu, Z., Zhao, H., and Agrawal, S. (1995) Pharmacokinetics and tissue distribution of a chimeric oligodeoxynucleotide phosphorothioate in rats following intravenous administration (unpublished results).Google Scholar
  34. 34.
    Zhang, R., Yan, J, Shahinian, H., Yan, J, Amin, G., Lu, Z, Jiang, Z, Temsamani, J., Saag, M S., Schechter, P. S, Agrawal, S, and Diasio, R B (1995) Human pharmacokinetics of an anti-HIV antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected individuals Clin Pharmacokinet Ther 58, 44–53CrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1996

Authors and Affiliations

  • Sudhir Agrawal
    • 1
  • Jamal Temsamani
    • 1
  1. 1.Hybridon, Inc.Worcester

Personalised recommendations