ArticleNucleic acids research2013
Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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106 citing papers in PubMed, 154 citations in OpenAlex.
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- HIV-1 Nef activates proviral DNA transcription by recruiting Src kinase to phosphorylate host protein Nef-associated factor 1 to compromise its viral restrictive function.Journal of virology · 2025Article
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- The Fourth Symposium of Grand Challenges on HIV (2023.12.28).Infectious diseases & immunity · 2024Article
- HIV-1 mRNA knockdown with CRISPR/CAS9 enhances neurocognitive function.Journal of neurovirology · 2024Article
- Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.Pathogens & immunity · 2024Article
- Navigating Latency-Inducing Viral Infections: Therapeutic Targeting and Nanoparticle Utilization.Biomaterials research · 2024Review
- Enhancing broadly neutralising antibody suppression of HIV by immune modulation and vaccination.Frontiers in immunology · 2024Review
- Article
- HIV-1 mRNA Knockdown with CRISPR/Cas9 Enhances Neurocognitive Function.Research square · 2023Article
- Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- An Evaluation on the Role of Non-Coding RNA in HIV Transcription and Latency: A Review.HIV/AIDS (Auckland, N.Z.) · 2023Review
- FBXO34 promotes latent HIV-1 activation by post-transcriptional modulation.Emerging microbes & infections · 2022Article
- Synaptic dysfunction is associated with alterations in the initiation of goal-directed behaviors: Implications for HIV-1-associated apathy.Experimental neurology · 2022Article
- Therapeutic Application of Genome Editing Technologies in Viral Diseases.International journal of molecular sciences · 2022Review
- Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.Pathogens (Basel, Switzerland) · 2021Review
- Article
- Broadly active zinc finger protein-guided transcriptional activation of HIV-1.Molecular therapy. Methods & clinical development · 2021Article
- Aristocratic human papillomavirus drove cervical cancer: a study of the therapeutic potential of the combination of interferon with zinc.Molecular and cellular biochemistry · 2021Review
- Inducible HIV-1 Reservoir Quantification: Clinical Relevance, Applications and Advancements of TILDA.Frontiers in microbiology · 2021Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-infected individuals currently cannot be completely cured because existing antiviral therapy regimens do not address HIV provirus DNA, flanked by long terminal repeats (LTRs), already integrated into host genome. Here, we present a possible alternative therapeutic approach to specifically and directly mediate deletion of the integrated full-length HIV provirus from infected and latently infected human T cell genomes by using specially designed zinc-finger nucleases (ZFNs) to target a sequence within the LTR that is well conserved across all clades. We designed and screened one pair of ZFN to target the highly conserved HIV-1 5'-LTR and 3'-LTR DNA sequences, named ZFN-LTR. We found that ZFN-LTR can specifically target and cleave the full-length HIV-1 proviral DNA in several infected and latently infected cell types and also HIV-1 infected human primary cells in vitro. We observed that the frequency of excision was 45.9% in infected human cell lines after treatment with ZFN-LTR, without significant host-cell genotoxicity. Taken together, our data demonstrate that a single ZFN-LTR pair can specifically and effectively cleave integrated full-length HIV-1 proviral DNA and mediate antiretroviral activity in infected and latently infected cells, suggesting that this strategy could offer a novel approach to eradicate the HIV-1 virus from the infected host in the future.
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