Abstract
Due to the increasing number of individuals with acquired immune deficiency syndrome (AIDS), considerable research efforts have focused on inhibiting replication of its causative agent, human immunodeficiency virus (HIV). Since the efforts of prophylactic vaccines have repeatedly failed, anti-viral strategies are now being aimed at direct inhibition of the virus or its replication. Infection by HIV leads to a progressive depletion of CD4+ cells of the immune system, resulting in the immunodeficiency associated with AIDS. HIV has proven a formidable therapeutic challenge for several reasons: (1) HIV permanently integrates its viral genome into the chromosomes of the host cell, (2) its primary targets are the cells of the body’s own defense system, namely, CD4+ T cells and macrophages, and (3) its genome is extremely plastic, undergoing high rates of mutation, thereby eluding the host’s immune system as well as potential vaccines and drug therapies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Akkina RK, Rosenblatt JD, Campbell AG, Chen ISY, Zack JA (1994) Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse. Blood 84: 1393–1398
Anderson P, Monforte J, Tritz R, Nesbitt S, Hearst J, Hampel A (1994) Mutagenesis of the hairpin ribozyme. Nucl Acids Res 22: 1096–1100
Baltimore D (1988) Gene therapy: intracellular immunization. Nature 335: 395–396
Berzal-Herranz A, Joseph S, Burke JM (1992) In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev 6: 129–134
Chatterjee S, Johnson PR, Wong KK (1992) Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. Science 258: 1485–1488
Cheong C, Varani G, Tinoco I (1990) Solution structure of an unusually stable RNA hairpin, 5’ GGAC(UUCG)GUCC. Nature 346: 680–682
Chowria BM, Beral-Herranz A, Burke JM (1993) Ionic requirements for RNA binding, cleavage and ligation by the hairpin ribozyme. Biochemistry 32: 1088–1095
Cotten M, Birnstiel ML (1989) Ribozyme-mediated destruction of RNA in vivo. EMBO J 8: 3861–3866
Fauci AS (1993) Multifactorial nature of HIV disease: implications for therapy. Science 262: 1011–1018
Folks TM, Kessler SW, Orenstein JM, Justement JS, Jaffe ES, Fauci AS (1988) Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science 242: 919–922
Hampel A, Tritz R (1989) RNA catalytic properties of the minimum (-)sTRSV sequence. Biochemistry 28: 4929–4933
Hampel A, Tritz R, Hicks M, Cruz P (1990) Hairpin catalytic RNA model: evidence for helices and sequence requirement for substrate RNA. Nucl Acids Res 18: 299–304
Jennings PA, Molloy PL (1987) Inhibition of SV40 replicon function by engineered antisense RNA transcribed by RNA polymerase III. EMBO J 6: 3043–3047
Joseph S, Berzal-Herranz A, Chowria BM, Butcher SE, Burke JM (1993) Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation and analysis of mismatched substrates. Genes Dev 7: 130–138
Leavitt MC, Yu M, Yamada O, Kraus G, Looney D, Poeschla E, Wong-Staal F (1994) Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes. Hum Gene Ther 5: 1115–1120
Lu M, Maruyama M, Zhang N, Lurine F, Friedmann T, Ho A (1994) High efficiency retroviral-mediated gene transduction into CD34+ cells purified from peripheral blood of breast cancer patients primed with chemotherapy and granulocyte-macrophage colony stimulatng factor. Hum Gene Ther 5: 203–208
Ojwang JO, Hampel A, Looney DJ, Wong-Staal F, Rappaport J (1992) Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci USA 89: 10802–10806
Steffy K, Wong-Staal F (1991) Genetic regulation of human immunodeficiency virus. Microbiol Rev 55: 193–205
Vaishnav YN, Wong-Staal F (1991) The biochemistry of AIDS. Annu Rev Biochem 60: 577–630
Yamada O, Kraus G, Leavitt MC, Yu M, Wong-Staal F (1994a) Activity and cleavage site specificity of an anti-HIV hairpin ribozyme in human T cells. Virology 205: 121–126
Yamada O, Yu M, Yee J-K, Kraus G, Looney D, Wong-Staal F (1994b) Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1. Gene Ther 1: 38–45
Yu M, Ojwang J, Yamada O, Hampel A, Rappaport J, Looney D, Wong-Staal F (1993) A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 90: 6340–6344
Yu M, Poeschla E, Wong-Staal F (1994) Progress toward gene therapy for HIV infection. Gene Ther 1: 13–26
Yu M, Leavitt MC, Maruyama M, Yamada O, Young D, Ho AD, Wong-Staal F (1995a) Intracellular immunization of human fetal cord blood stem/progenitor cells with a ribozyme against human immunodeficiency virus type 1. Proc Natl Acad Sci USA 92: 699–703
Yu M, Poeschla E, Yamada O, Degrandis P, Leavitt MC, Heusch M, Yee J-K, Wong-Staal F, Hampel A (1995b) In vitro and in vivo characterization of a second functional hairpin ribozyme against HIV-1. Virology 206: 381–386
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Welch, P.J., Hampel, A., Barber, J., Wong-Staal, F., Yu, M. (1996). Inhibition of HIV Replication by the Hairpin Ribozyme. In: Eckstein, F., Lilley, D.M.J. (eds) Catalytic RNA. Nucleic Acids and Molecular Biology, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61202-2_18
Download citation
DOI: https://doi.org/10.1007/978-3-642-61202-2_18
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-62679-4
Online ISBN: 978-3-642-61202-2
eBook Packages: Springer Book Archive