ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- What's Hot in HIV in 2025-A Basic and Translational Science Review From IDWeek 2025.The Journal of infectious diseases · 2026Review
- CRISPR Applications in HIV Management - Prevention, Diagnosis, Monitoring and Treatment.Current HIV/AIDS reports · 2026Review
- CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025Review
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- HIV-1 Tat: Molecular Switch in Viral Persistence and Emerging Technologies for Functional Cure.International journal of molecular sciences · 2025Review
- Efficient mRNA delivery to resting T cells to reverse HIV latency.Nature communications · 2025Article
- Article
- Review
- HIV cure research contributions from Africa in the last three decades.Frontiers in immunology · 2025Review
- Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.Molecular biotechnology · 2024Review
- Epigenome editing technologies for discovery and medicine.Nature biotechnology · 2024Review
- Review
- Review
- Targeting Viral Transcription for HIV Cure Strategies.Microorganisms · 2024Review
- Gesicles packaging dCas9-VPR ribonucleoprotein complexes can combine with vorinostat and promote HIV proviral transcription.Molecular therapy. Methods & clinical development · 2024Article
- Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery.Gene therapy · 2024Article
- CRISPR Activation in Mouse Trophoblast Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- CRISPR/dCas9 Tools: Epigenetic Mechanism and Application in Gene Transcriptional Regulation.International journal of molecular sciences · 2023Review
- Automated microarray platform for single-cell sorting and collection of lymphocytes following HIV reactivation.Bioengineering & translational medicine · 2023Article
- Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
HIV-1 provirus integration results in a persistent latently infected reservoir that is recalcitrant to combined antiretroviral therapy (cART) with lifelong treatment being the only option. The "shock and kill" strategy aims to eradicate latent HIV by reactivating proviral gene expression in the context of cART treatment. Gene-specific transcriptional activation can be achieved using the RNA-guided CRISPR-Cas9 system comprising single guide RNAs (sgRNAs) with a nuclease-deficient Cas9 mutant (dCas9) fused to the VP64 transactivation domain (dCas9-VP64). We engineered this system to target 23 sites within the long terminal repeat promoter of HIV-1 and identified a "hotspot" for activation within the viral enhancer sequence. Activating sgRNAs transcriptionally modulated the latent proviral genome across multiple different in vitro latency cell models including T cells comprising a clonally integrated mCherry-IRES-Tat (LChIT) latency system. We detected consistent and effective activation of latent virus mediated by activator sgRNAs, whereas latency reversal agents produced variable activation responses. Transcriptomic analysis revealed dCas9-VP64/sgRNAs to be highly specific, while the well-characterized chemical activator TNFα induced widespread gene dysregulation. CRISPR-mediated gene activation represents a novel system which provides enhanced efficiency and specificity in a targeted latency reactivation strategy and represents a promising approach to a "functional cure" of HIV/AIDS.
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Registered trials
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