Catalytic Antisense RNA (Ribozymes): Their Potential and Use as ANTI-HIV-1 Therapeutic Agents

  • John J. Rossi
  • Nava Sarver
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 312)


Catalytic RNAs were first discovered as natural processes in several biological systems 1,2,3.Their discovery is one of the landmark accomplishments of modern science since it was the first demonstration that an informational molecule could also possess enzymatic activity, and hence changed our views on the possible origins of life. The discovery and characterization of the reactions carried out by RNA molecules has facilitated the development of an entirely distinct approach to antiviral therapy, the site specific, cleavage of viral RNAs mediated by catalytic, anti-sense ribozymes. We are using ribozymes as a novel antiviral strategy. In the following paragraphs, we weill describe the development of anti-sense ribozymes with the primary emphasis being their application as anti-HIV-1 therapeutic agents.


Cleavage Product Cleavage Reaction Hammerhead Ribozyme Catalytic Active Center Ribozyme Cleavage 
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  1. 1.
    Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E., Cech, T.R., 1982, Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena, Cell 31:147.CrossRefPubMedGoogle Scholar
  2. 2.
    Takada, C.G., Gardiner, K., Marsh, T., Pace, N., Altman, S., 1983, The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849.CrossRefGoogle Scholar
  3. 3.
    Forster, A., Symons, R.H., 1987, Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active site, Cell 49:211.CrossRefPubMedGoogle Scholar
  4. 4.
    Epstein, L.M., Gall, J., 1987, Transcripts of newt satellite DNA autocleave in vitro, Cold Spring Harbor Symp. Quant. Biol. 52:261.CrossRefPubMedGoogle Scholar
  5. 5.
    Fedor, M., Uhlenbeck, O.C., 1990, Substrate sequence effects on “hammerhead” RNA catalytic efficiency, Proc. Nat. Acad. Sci. USA 87:1668.CrossRefPubMedGoogle Scholar
  6. 6.
    Uhlenbeck, O.C., 1987, A small catalytic oligoribonucleotide, Nature 328:596.CrossRefPubMedGoogle Scholar
  7. 7.
    Haseloff, J., Gerlach, W.L., 1988, Simple RNA enzymes with new and highly specific endoribonuclease activity, Nature 334:585.CrossRefPubMedGoogle Scholar
  8. 8.
    Ruffner, D.E., Stormo, G.D., Uhlenbeck, O.C., 1990, Sequence requirements of the hammerhead RNA self-cleavage reaction, Biochemistry 29:10695.CrossRefPubMedGoogle Scholar
  9. 9.
    Chang, P.S., Cantin, E.M., Zaia, J.A., Ladne, P.A., Stephens, D.A., Sarver, N., Rossi, J.J., 1990, Ribozyme-mediated site-specific cleavage of the HIV-1 genome, Clinical Biotechnology 2:23.Google Scholar
  10. 10.
    Rossi, J.J., Cantin, E.M., Zaia, J.A., Ladne, P.A., Chen, J., Stephens, D.A., Sarver, N., Chang, P.S., 1990, Ribozymes as therapies for AIDS, AIDS: anti-HIV agents, therapies and vaccines, Annals of the N.Y. Acad. Sci. 616:184.CrossRefGoogle Scholar
  11. 11.
    Sarver, N., Cantin, E., Chang, P., Ladne, P., Stephens, D., Zaia, J., Rossi, J.J., 1990, Ribozymes as potential anti-HIV-1 therapeutic agents, Science 247:1222.CrossRefPubMedGoogle Scholar
  12. 12.
    Saiki, R.K., Scharf, S., Faloona, F., Mullis, K., Horn, G., Erlich, A., Arnheim, N., 1985, Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia, Science 230:1350.CrossRefPubMedGoogle Scholar
  13. 13.
    Leonetti, J., Machy, P., Degols, G., Lebleu, B., and Leserman, L., 1990, Antibody targeted liposomes containing oligodeoxyribonucleotides complementary to viral RNA selectively inhibit viral replication, Proc. Natl. Acad. Sci. USA 87:2448.CrossRefPubMedGoogle Scholar
  14. 14.
    Chatterjee, S., Wong, K.K., Rose, J.A., Johnson, P.R., 1991, Transduction of intracellular resistance to HIV production by an adeno-associated virus-based antisense vector. IN: Vaccine 91: Modern approaches to new vaccines including the prevention of AIDS. R.M. Channock, H.S. Ginberg, F. Brown and R.A. Lerner, eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.Google Scholar
  15. 15.
    Riesner, D., Gross, H.J., 1985, Viroids, Ann. Rev. Biochem. 54:531.CrossRefPubMedGoogle Scholar
  16. 16.
    Kotin, R.M., Siniscalo, M., Samulshi, J., Zhu, X., Hunter, L., Laughlin, C., McLaughlin, S., Mazycka, N., Rocchi, M., Berns, K.I., 1990, Site-specific integration by adeno-associated virus, PNAS 87:2211.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • John J. Rossi
    • 1
  • Nava Sarver
    • 2
  1. 1.Department of Molecular Genetics, Beckman ResearchInstitute of the City of HopeDuarteUSA
  2. 2.Developmental Therapeutics BranchDivision of AIDS, NIAIDBethesdaUSA

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