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The therapeutic landscape of HIV-1 via genome editing

Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infe...

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Autores principales: Kwarteng, Alexander, Ahuno, Samuel Terkper, Kwakye-Nuako, Godwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513397/
https://www.ncbi.nlm.nih.gov/pubmed/28705213
http://dx.doi.org/10.1186/s12981-017-0157-8
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author Kwarteng, Alexander
Ahuno, Samuel Terkper
Kwakye-Nuako, Godwin
author_facet Kwarteng, Alexander
Ahuno, Samuel Terkper
Kwakye-Nuako, Godwin
author_sort Kwarteng, Alexander
collection PubMed
description Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing  perspectives for refining these techniques.
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spelling pubmed-55133972017-07-19 The therapeutic landscape of HIV-1 via genome editing Kwarteng, Alexander Ahuno, Samuel Terkper Kwakye-Nuako, Godwin AIDS Res Ther Review Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing  perspectives for refining these techniques. BioMed Central 2017-07-14 /pmc/articles/PMC5513397/ /pubmed/28705213 http://dx.doi.org/10.1186/s12981-017-0157-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Kwarteng, Alexander
Ahuno, Samuel Terkper
Kwakye-Nuako, Godwin
The therapeutic landscape of HIV-1 via genome editing
title The therapeutic landscape of HIV-1 via genome editing
title_full The therapeutic landscape of HIV-1 via genome editing
title_fullStr The therapeutic landscape of HIV-1 via genome editing
title_full_unstemmed The therapeutic landscape of HIV-1 via genome editing
title_short The therapeutic landscape of HIV-1 via genome editing
title_sort therapeutic landscape of hiv-1 via genome editing
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513397/
https://www.ncbi.nlm.nih.gov/pubmed/28705213
http://dx.doi.org/10.1186/s12981-017-0157-8
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