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RNAi-Inducing Lentiviral Vectors for Anti-HIV-1 Gene Therapy

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Antiviral RNAi

Part of the book series: Methods in Molecular Biology ((MIMB,volume 721))

Abstract

RNA interference (RNAi)-based gene therapy for the treatment of HIV-1 infection provides a novel antiviral approach. For delivery of RNAi inducers to CD4+ T cells or CD34+ blood stem cells, lentiviral vectors are attractive because of their ability to transduce nondividing cells. In addition, lentiviral vectors allow stable transgene expression by inserting their cargo into the host cell genome. However, use of the HIV-1-based lentiviral vector also creates specific problems. The RNAi inducers can target HIV-1 sequences in the genomic RNA of the lentiviral vector. As the RNAi-inducing cassette contains palindromic sequences, the lentiviral vector RNA genome will have a perfect target sequence for the expressed RNAi inducer. Vectors encoding microRNAs face the putative problem that the vector RNA genome can be inactivated by Drosha processing. Here, we describe the design of lentiviral vectors with single or multiple RNAi-inducing antiviral cassettes. The possibility of titer reduction and some effective countermeasures are also presented.

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Authors and Affiliations

  1. Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Ying Poi Liu

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  1. Ying Poi Liu
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  2. Jan-Tinus Westerink
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  3. Olivier ter Brake
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  4. Ben Berkhout
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Correspondence to Ying Poi Liu .

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Editors and Affiliations

  1. Inst. for Infection, Inflammation & Immu, Dept. Medical Microbiology, Radboud Univ.Nijmegen Medical Ctr, Geert Grooteplein 28, Nijmegen, 6525 GA, Netherlands

    Ronald P. van Rij

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© 2011 Humana Press

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Liu, Y.P., Westerink, JT., ter Brake, O., Berkhout, B. (2011). RNAi-Inducing Lentiviral Vectors for Anti-HIV-1 Gene Therapy. In: van Rij, R. (eds) Antiviral RNAi. Methods in Molecular Biology, vol 721. Humana Press. https://doi.org/10.1007/978-1-61779-037-9_18

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  • DOI: https://doi.org/10.1007/978-1-61779-037-9_18

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  • Print ISBN: 978-1-61779-036-2

  • Online ISBN: 978-1-61779-037-9

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