The therapeutic landscape of HIV-1 via genome editing.
Identifieur interne : 000008 ( Main/Exploration ); précédent : 000007; suivant : 000009The therapeutic landscape of HIV-1 via genome editing.
Auteurs : Alexander Kwarteng [Ghana] ; Samuel Terkper Ahuno [Ghana] ; Godwin Kwakye-Nuako [Ghana]Source :
- AIDS research and therapy [ 1742-6405 ] ; 2017.
Abstract
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.
DOI: 10.1186/s12981-017-0157-8
PubMed: 28705213
Affiliations:
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type="wicri:Area/Main/Exploration">000008</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The therapeutic landscape of HIV-1 via genome editing.</title><author><name sortKey="Kwarteng, Alexander" sort="Kwarteng, Alexander" uniqKey="Kwarteng A" first="Alexander" last="Kwarteng">Alexander Kwarteng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), PMB, Kumasi, Ghana. akwarteng@knust.edu.gh.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), PMB, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Ahuno, Samuel Terkper" sort="Ahuno, Samuel Terkper" uniqKey="Ahuno S" first="Samuel Terkper" last="Ahuno">Samuel Terkper Ahuno</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), PMB, Kumasi, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), PMB, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Kwakye Nuako, Godwin" sort="Kwakye Nuako, Godwin" uniqKey="Kwakye Nuako G" first="Godwin" last="Kwakye-Nuako">Godwin Kwakye-Nuako</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical Sciences, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Biomedical Sciences, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast</wicri:regionArea><wicri:noRegion>Cape Coast</wicri:noRegion></affiliation></author></analytic><series><title level="j">AIDS research and therapy</title><idno type="eISSN">1742-6405</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. 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