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Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides

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Abstract

We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5′ end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3′ end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.

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References

  1. Knorre D.G. and Vlassov V.V., Prog Nucleic Acids Res Mol Biol32 291–320, 1985.

    Google Scholar 

  2. Hélène C., C R Vie Sci Ser Gen4 17–37, 1987.

    Google Scholar 

  3. Stein C.A. and Cohen J.S., Cancer Res48 3355–3359, 1988.

    Google Scholar 

  4. Vlassov V.V., Godovikov A.A., Kobetz N.D., Ryte A.S., Yurchenko L.V., and Bukrinskaya A.G., Adv Enzyme Regul24 301–322, 1985.

    Google Scholar 

  5. Calabretta B., Cancer Res51 4505–4510, 1991.

    Google Scholar 

  6. Saison-Behmoaras T., Tocque B., Rey I., Chassignol M., Thuong N.T., and Hélène C., EMBO J10 1111–1118, 1991.

    Google Scholar 

  7. Workman P., D'Incalci M., Berdel W.E., Egorin M.J., Hélène C., Hickman J.A., Jarman M., Schwartsmann G., and Sikora K., Eur J Cancer28A 1190–1200, 1992.

    Google Scholar 

  8. McManaway M.E., Neckers L.M., Loke S.L. et al., Lancet335 808–811, 1990.

    Google Scholar 

  9. Whitesell L., Rosolen A., and Neckers L.M., Mol Cell Biol11 1360–1370, 1991.

    Google Scholar 

  10. Melani C., Rivoltini L., Parmiani G., Calabretta B., and Colombo M.P., Cancer Res51 2897–2901, 1991.

    Google Scholar 

  11. Szczylik C., Skorski T., Nicolaides N.C., et al., Science253 562–568, 1991.

    Google Scholar 

  12. Gutierrez A.A., Lemoine N.R., and Sikora K., Lancet339 715–721, 1992.

    Google Scholar 

  13. Zamecnik P. and Stephenson M.L., Proc Natl Acad Sci USA75 280–284, 1978.

    Google Scholar 

  14. Agris C.H., Blake K.R., Miller P.S., Reddy M.P., and T'so P.O.P., Biochemistry25 6268–6275, 1986.

    Google Scholar 

  15. Lemaitre M., Bisbal C., and Lebleu B., Proc Natl Acad Sci USA84 648–652, 1987.

    Google Scholar 

  16. Kulka M., Smith C.C., Aurelian L., Fishelevitch R., Meade K., Miller P., and T'so P.O.P., Proc Natl Acad Sci USA86 6868–6872, 1990.

    Google Scholar 

  17. Birg F., Praseuth D., Zerial A., Thuong N.T., Asseline U., Le Doan T., and Hélène C., Nucleic Acids Res18 2901–2908, 1990.

    Google Scholar 

  18. Zerial A., Thuong N.T., and Hélène C., Nucleic Acids Res15 9909–9919, 1987.

    Google Scholar 

  19. Zamecnik P.C., Goodchild J., Taguchi, and Sarin P.S., Proc Natl Acad Sci USA83 4143–4146, 1986.

    Google Scholar 

  20. Matsukara M., Shinozuka K., Zon G., Mitsuya H., Reitz M., Cohen J.S., and Broder S., Proc Natl Acad Sci USA84 7706–7710, 1987.

    Google Scholar 

  21. Goodchild J., Agrawal S., Civeira M.P., Sarin P.S., Sun D., and Zamecnik P.C., Proc Natl Acad Sci USA85 5507–5511, 1988.

    Google Scholar 

  22. Agrawal S., Ikeuchi T., Sun D., Sarin P.S., Konopka A., and Maizel J., Proc Natl Acad Sci USA86 7790–7794, 1989.

    Google Scholar 

  23. Mori K., Boiziau C., Cazenave C., Matsukura M., Subasinghe C., Cohen J.S., Broder S., Toulm' J.J., and Stein C.A., Nucleic Acids Res17 8207–8219, 1989.

    Google Scholar 

  24. Sarin P.S., Agrawal S., Civeira M.P., Goodchild J., Ikeuchi T., and Zamecnik P.C., Proc Natl Acad Sci USA85 7448–7451, 1988.

    Google Scholar 

  25. Zaia J.A., Rossi J.J., Murakawa G.J., Spallone P.A., Stephens D.A., and Kaplan B.E., J Virol62 3914–3917, 1988.

    Google Scholar 

  26. Stevenson M. and Iversen P.L., J Gen Virol70 2673–2682, 1989.

    Google Scholar 

  27. Laurence J., Sikder S.K., Kulkosky J., Miller P., and Ts'o P.O.P., J Virol65 213–219, 1991.

    Google Scholar 

  28. Agrawal S., Goodchild J., Civeira M.P., Thornton A.H., Sarin P.S., and Zamecnik P.C., Proc Natl Acad Sci USA85 7079–7083, 1988.

    Google Scholar 

  29. Matsukura M., Zon G., Shinizuka K., Robert-Guroff M., Shimida T., and Stein C.A., Proc Natl Acad Sci USA86 4244–4248, 1989.

    Google Scholar 

  30. Majumdar C., Stein C.A., Cohen J.S., Broder S., and Wilson S.H., Biochemistry28 1340–1346, 1989.

    Google Scholar 

  31. Iyer R.P., Uznanski B., Boal J., Storn C., Egan W., Matsukura M., Broder S., Zon G., Wilk A., Koziolkiewicz M., and Stec W.J., Nucleic Acids Res18 2855–2859, 1990.

    Google Scholar 

  32. Letsinger R.L., Zhang G.R., Sun D.K., Ikeuchi T., and Sarin P.S., Proc Natl Acad Sci USA86 6553–6556, 1989.

    Google Scholar 

  33. Bordier B., Hélène C., Barr P.J., Litvak S., and Sarih-Cottin L., Nucleic Acids Res20 5999–6006, 1992.

    Google Scholar 

  34. Hatta T., Kim S.-G., Nakashima H., Yamamoto M., Sakamoto K., Yokohama S., and Takaku H., FEBS Lett330 161–164, 1993.

    Google Scholar 

  35. Vickers T., Baker B.F., Cook P.D., Zounes M., Buckheit R.W., Jr., Germany J., and Ecker D.J., Nucleic Acids Res19 3359–3368, 1991.

    Google Scholar 

  36. Arya S.K., Guo C., Josephs S.F., and Wong-Staal F., Science229 69–73, 1985.

    Google Scholar 

  37. Chandra A., Demirhan I., Arya S.K., and Chandra P., FEBS Lett236 282–286, 1988.

    Google Scholar 

  38. Arya S.K. and Gallo R.C., Proc Natl Acad Sci USA83 2209–2213, 1986.

    Google Scholar 

  39. Zarytova V.F., Ivanova E.M., and Romanenko V.P., Bioorg Khim (USSR)9 516–521, 1983.

    Google Scholar 

  40. Bausk E.V., Gorn V.V., and Lebedev A.V., Bioorg Khim (USSR)11 815–820, 1985.

    Google Scholar 

  41. Dobrynin V.N., Bystrov N.S., Chernov B.K., Severtzeva I.V., and Kolosov M.N., Bioorg Khim (USSR)5 1254–1256, 1979.

    Google Scholar 

  42. Boutorin A.S., Gus'kova L.V., Ivanova E.M., Kobetz N.D., Zarytova V.F., Ryte A.S., Yurchenko L.V., and Vlassov V.V., FEBS Lett254 129–132, 1989.

    Google Scholar 

  43. Cullen B.R., Microbiol Rev56 375–394, 1992.

    Google Scholar 

  44. Viscidi R.P., Mayur K., Lederman H.M., and Frankel A.D., Science246 1606–1608, 1989.

    Google Scholar 

  45. Vogel J., Hinrichs S.H., Reynolds R.K., Luciw P.A., and Jay G., Nature335 606–611, 1988.

    Google Scholar 

  46. Ensoli B., Barillari G., Salahuddin S.Z., Gallo R.C., and Wong-Staal F., Nature345 84–86, 1990.

    Google Scholar 

  47. Chandra P., Chandra A., Gerber T., and Demirhan I. in Schauzu M. (ed).Progress in AIDS Research in the Federal Republic of Germany. MMV-Medizin Verlag, Munich, 1990, pp. 213–226.

    Google Scholar 

  48. Chandra P., Chandra A., Demirhan I., and Gerber T. in Borowsky E. and Shugar D. (eds). Pharmacology and Therapeutics Supplement, Pergamon Press, New York, pp. 25–46.

  49. Chandra A., Demirhan I., Arya S.K., and Chandra P., FEBS Lett236 282–286, 1988.

    Google Scholar 

  50. Hofmann D., Chandra A., Demirhan I., and Chandra P., VII. International Conference on AIDS, Florence (16–21, June 1991), abstract WA 1063.

  51. Chandra P., Gerber T., and Chandra A., FEBS Lett268 415–421, 1990.

    Google Scholar 

  52. Demirhan I., Chandra A., Hofmann D., and Chandra P., Zeitschr Antimikrob Antineopl Chemoth10 75–79, 1992.

    Google Scholar 

  53. Hsu M.C., Schutt A.D., Holly M., Slice L.W., Sherman M.I., Richmann D.D., Potash M.J., and Volsky D.J., Science254 1799–1802, 1991.

    Google Scholar 

  54. Braddock M., Thorburn A.M., Chambers A., Elliott G.D., Anderson G.J., Kingsman A.J., and Kingsman S.M., Cell62 1123–1133, 1990.

    Google Scholar 

  55. Daefler S., Klotman M.E., and Wong-Staal F., Proc Natl Acad Sci USA87 4571–4575, 1990.

    Google Scholar 

  56. Davis J.L. and Clements J.E., Proc Natl Acad Sci USA86 414–418, 1989.

    Google Scholar 

  57. Ensoli B., Buonaguro J., Barillary D., Fiorelli V., Gendelman R., Morgan R.A., Wingfield P., and Gallo R.C., J Virol67 277–287, 1993.

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Frankfurt University School of Medicine, 60590, Frankfurt, FRG

    I. Demirhan, O. Hasselmayer, D. Hofmann, A. Chandra &  P. Chandra (Head of Molecular Biology (ZBC)

  2. Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences, Novosibirsk

    F. P. Svinarchuk & V. V. Vlassov

  3. Institute of Organic Chemistry, Frankfurt University, FRG

    J. Engels

Authors
  1. I. Demirhan
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  2. O. Hasselmayer
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  3. D. Hofmann
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  4. A. Chandra
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  5. F. P. Svinarchuk
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  6. V. V. Vlassov
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  7. J. Engels
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  8. P. Chandra
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Dedicated to Professor Klaus Ring on his 60th birthday.

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Demirhan, I., Hasselmayer, O., Hofmann, D. et al. Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides. Virus Genes 9, 113–119 (1995). https://doi.org/10.1007/BF01702654

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  • DOI: https://doi.org/10.1007/BF01702654

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