Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors. These mechanisms attack different forms of the viral genome, the RNA and DNA, respectively, but both mechanisms act in a strictly sequence-specific manner. Early RNAi experiments demonstrated profound virus inhibition, but also indicated that viral escape is possible. Such therapy failure can be prevented by the design of a combinatorial RNAi attack on the virus and this gene therapy is currently being tested in a preclinical humanized mouse model. Recent CRISPR-Cas studies also document robust virus inhibition, but suggest a novel viral escape route that is induced by the cellular nonhomologous end joining DNA repair pathway, which is activated by CRISPR-Cas-induced DNA breaks. We will compare these two approaches for durable HIV-1 suppression and discuss the respective advantages and disadvantages. The potential for future clinical applications will be described.
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October 2016
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Alternative splicing of intrinsically disordered segments can rewire protein interaction networks. In this issue, the Biochemical Society’s Colworth Medal winner, M. Madan Babu explores the contribution of intrinsically disordered regions to protein function, cellular complexity and human disease; see pages 1185–1200. [Credit: Guilhem Chalancon, MRC Laboratory of Molecular Biology, Cambridge, UK.]
Review Article|
October 19 2016
Attacking HIV-1 RNA versus DNA by sequence-specific approaches: RNAi versus CRISPR-Cas
Elena Herrera-Carrillo;
Elena Herrera-Carrillo
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands
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Ben Berkhout
Ben Berkhout
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands
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Publisher: Portland Press Ltd
Received:
February 12 2016
Revision Received:
June 09 2016
Accepted:
June 21 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem Soc Trans (2016) 44 (5): 1355–1365.
Article history
Received:
February 12 2016
Revision Received:
June 09 2016
Accepted:
June 21 2016
Citation
Elena Herrera-Carrillo, Ben Berkhout; Attacking HIV-1 RNA versus DNA by sequence-specific approaches: RNAi versus CRISPR-Cas. Biochem Soc Trans 15 October 2016; 44 (5): 1355–1365. doi: https://doi.org/10.1042/BST20160060
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