Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jul 14;14(1):32.
doi: 10.1186/s12981-017-0157-8.

The therapeutic landscape of HIV-1 via genome editing

Alexander Kwarteng  1   2 , Samuel Terkper Ahuno  3 , Godwin Kwakye-Nuako  4
Affiliations
Review

The therapeutic landscape of HIV-1 via genome editing

Alexander Kwarteng et al. AIDS Res Ther. .

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Zinc finger nucleases
Fig. 2
Fig. 2
TALENS
Fig. 3
Fig. 3
CRISPR–Cas9
Fig. 4
Fig. 4
DNA repair mechanism
Fig. 5
Fig. 5
In vivo and ex vivo delivery methods
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet. 2014;384(9939):258–271. doi: 10.1016/S0140-6736(14)60164-1. - DOI - PubMed
    1. United Nations Programme on HIV/AIDS . AIDS by the numbers. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2016. - PubMed
    1. Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, Chomont N, Douek D, Lifson JD, Lo YR, et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat Med. 2016;22(8):839–850. doi: 10.1038/nm.4108. - DOI - PMC - PubMed
    1. Bartholomeeusen K, Xiang Y, Fujinaga K, Peterlin BM. Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein. J Biol Chem. 2012;287(43):36609–36616. doi: 10.1074/jbc.M112.410746. - DOI - PMC - PubMed
    1. Yu W, Ramakrishnan R, Wang Y, Chiang K, Sung TL, Rice AP. Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors. PLoS ONE. 2008;3(9):e3146. doi: 10.1371/journal.pone.0003146. - DOI - PMC - PubMed

MeSH terms

Substances