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Antisense-Mediated Inhibition of Protein Synthesis

Rational Drug Design, Pharmacokinetics, Intracerebral Application, and Organ Uptake of Phosphorothioate Oligodeoxynucleotides

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Antisense Therapeutics

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 1))

Abstract

There is hardly any class of drugs for which the term “ratronal drug design” is more appropriate than for the currently developing antisense therapeutics. The specrficlty of the hybridization reaction and the surprisingly efficient uptake of synthetrc oligonucleotide derivatives provide a new class of selective protein synthesis inhibitors. Concurrently with the development of the antisense technology, elucidation of the pathogenetic role of mdrvrdual proteins for certain diseases is rapidly progressing, most notably in the fields of cancer research and virology. Consequently, the first clinical trtals are being conducted with antrsense therapeutics for the treatment of viral diseases and neoplasms.

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References

  1. Stephenson, M and Zamecmk, P. C (1978) Inhibition of Rous sarcoma viral RNA translation by a specific ohgodeoxyrlbonucleotlde Proc Natl Acad Scz USA 75, 285–288.

    Article  CAS  Google Scholar 

  2. Zamecmk, P C and Stephenson, M (1978) InhibitIon of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotlde Proc Natl Acad Scz. USA 75, 280–284.

    Article  Google Scholar 

  3. Campbell, J, Bacon, T, and Wickstrom, E (1990) Ohgodeoxynucleoside phosphorothloate stabilrty in subcellular abstracts, culture media, sera and cerebrospmal fluid. J. Blochem Biophys Methods 20, 259–267

    Article  CAS  Google Scholar 

  4. Eckstem, F (1983) Phosphorothioate analogues of nucleotldes-tools for the investigation of blochemlcal processes. Angewandte Chemle 22, 423–506.

    Article  Google Scholar 

  5. Stem, C A and Cheng, Y C (1993) Antisense ohgonucleotldes as therapeutic agents—is the bullet really magical? Sczence 261, 1004–1012

    Google Scholar 

  6. Bishop, J. M (1991) Molecular themes in oncogenesls Cell 64, 235–248

    Article  PubMed  CAS  Google Scholar 

  7. Griffin, J. P, O’Grady, J, and Wells, F O (eds.) (1993) The Textbook of Pharmaceutical Medicine The Queen’s University of Belfast, Belfast.

    Google Scholar 

  8. Zuker, M. and Stlegler, P. (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information Nucleic Acids Res 9, 133–148

    Article  PubMed  CAS  Google Scholar 

  9. Schevltz, R W, Podjarny, A D., Krishnamachan, N., Hughes, J. J., Sigler P B., and Sussman, J L (1979) Crystal structure of an eukaryotlc initiator tRNA Nature 278, 188–190

    Article  Google Scholar 

  10. Schlingensiepen, K.-H., Schlingensiepen, R., Kunst, M., Klinger, I., Gerdes, W., Seifert, W., and Brysch W (1993) Opposite functions of Jun-B and c-Jun in growth regulation and neuronal differentiation. Dev Genet 14, 305–312.

    Article  PubMed  CAS  Google Scholar 

  11. Jachlmczak, P, Bogdahn, U., Schneider, J., Behl, C., Meixensberger, J, Apfel, R, Domes, R, Schlingenslepen, K.-H., and Brysch W. (1993) TGF-P2-specific phosphorothloate antlsense oligodeoxynucleotides may reverse cellular immunosuppression in malignant ghoma J Neurosurg 78, 944–951

    Article  Google Scholar 

  12. Vogt, P. K. and Bos, T J (1990) jun’ oncogene and transcrlption factor Adv Cancer Res 55, 1–35

    Article  PubMed  CAS  Google Scholar 

  13. Enkson, R. L (1991) Structure, expression and regulation of protein kmases involved in the phosphorylation of ribosomal S6 J Biol Chem 266, 6007–6009

    Google Scholar 

  14. Bravo, R. (1990) Genes induced during the G0/G1 transitron in mouse tibroblasts Semm Cancer Biol 1, 37–46

    CAS  Google Scholar 

  15. Sheng, M and Greenberg, M E (1990) The regulation and function of c-fos and other munedrate early genes in the nervous system Neuron 4, 477–485

    Article  PubMed  CAS  Google Scholar 

  16. Toulme, J-J and Helene, C (1988) Anttmessenger ohgodeoxyrtbonucleotrdes an alternatrve to antrsense RNA for artrficial regulation of gene expression Gene 72, 51–58

    Article  PubMed  CAS  Google Scholar 

  17. Becker, D., Merer, C B, and Herlyn, M (1989) Proliferation of human melanomas 1s inlibited by antisense olrgodeoxynucleotrdes against basic fibroblast growth factor EMBO J 8, 3685–3691

    PubMed  CAS  Google Scholar 

  18. Kim, S J., Park, K, Koeller, D., Kim, K. Y., Wakefield, L. M., Sporn, M B, and Roberts, A B (1992) Post-transcriptional regulatron of the human transforming growth factor-beta 1 gene. J Biol Chem 267, 13,702–13,707

    PubMed  CAS  Google Scholar 

  19. Romeo, D S, Park, K., Roberts, A. B, Spom, M B., and Kim, S J. (1993) An element of the transforming growth factor-beta 1 5′-untranslated region represses translatron and spectfically binds a cytosohc factor. Mol Endocrinol 7, 759–766

    Article  PubMed  CAS  Google Scholar 

  20. Agrawal, S, Temsamam, J, and Tang, J Y (1991) Pharmacoklnetics, btodrstrrbutron, and stabthty of ohgodeoxynucleotrde phosphorothroates in mice Proc Natl Acad SCI USA 88, 7595–7599.

    Article  PubMed  CAS  Google Scholar 

  21. Behl, C, Bogdahn, U, Wmkler, J., Metxensberger, J, Schlingenslepen, K-H, and Brysch, W (1993) Autocrme growth regulation in neuroectodermal tumors as detected with ohgodeoxynucleotrde antisense molecules Neurosurgery 33, 679–684

    Article  PubMed  CAS  Google Scholar 

  22. Schlingensrepen, K-H, Wollmk, F., Kunst, M., Schlingensrepen, R, Herdegen, T, and Brysch, W (1994) The role of jun transcnption factor expression and phosphorylation in neuronal drfferentratron, neuronal cell death and in plastic adaptations in vivo Cell Mol Neurobiol 14, 487–505

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Max-Planck Institute for Biophysical Chemistry, Gottingen, Germany

    Wolfgang Brysch, Abdalla Rifai, Wolfgang Tischmeyer & Karl-Hermann Schlingensiepen

Authors
  1. Wolfgang Brysch
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  2. Abdalla Rifai
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  3. Wolfgang Tischmeyer
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  4. Karl-Hermann Schlingensiepen
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Editor information

Editors and Affiliations

  1. Hybridon, Inc., Worcester, MA

    Sudhir Agrawal

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© 1996 Humana Press Inc., Totowa, NJ

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Brysch, W., Rifai, A., Tischmeyer, W., Schlingensiepen, KH. (1996). Antisense-Mediated Inhibition of Protein Synthesis. In: Agrawal, S. (eds) Antisense Therapeutics. Methods in Molecular Medicine, vol 1. Humana Press. https://doi.org/10.1385/0-89603-305-8:159

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  • DOI: https://doi.org/10.1385/0-89603-305-8:159

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-305-4

  • Online ISBN: 978-1-59259-585-3

  • eBook Packages: Springer Protocols

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