ArticleBMC medical genomics2018
Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling.
Article in BMC medical genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Regulatory roles of LncRNAs in colorectal cancer immune evasion: current concepts and future perspectives.Discover oncology · 2025Review
- Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025Review
- Seed sequences mediate off-target activity in the CRISPR-interference system.Cell genomics · 2024Article
- Article
- Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery.Gene therapy · 2024Article
- Lnc_000048 Promotes Histone H3K4 Methylation of MAP2K2 to Reduce Plaque Stability by Recruiting KDM1A in Carotid Atherosclerosis.Molecular neurobiology · 2023Article
- Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer.Cancers · 2023Article
- Strategies for HIV-1 suppression through key genes and cell therapy.Frontiers in medicine · 2023Review
- Updates on CRISPR-based gene editing in HIV-1/AIDS therapy.Virologica Sinica · 2022Review
- Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.Pathogens (Basel, Switzerland) · 2021Review
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- Europium sulfide nanoprobes predict antiretroviral drug delivery into HIV-1 cell and tissue reservoirs.Nanotheranostics · 2021Article
- CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off-Target Evaluation, and Strategies to Mitigate Off-Target Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCRISPR/CAS9 (epi)genome editing revolutionized the field of gene and cell therapy. Our previous study demonstrated that a rapid and robust reactivation of the HIV latent reservoir by a catalytically-deficient Cas9 (dCas9)-synergistic activation mediator (SAM) via HIV long terminal repeat (LTR)-specific MS2-mediated single guide RNAs (msgRNAs) directly induces cellular suicide without additional immunotherapy. However, potential off-target effect remains a concern for any clinical application of Cas9 genome editing and dCas9 epigenome editing. After dCas9 treatment, potential off-target responses have been analyzed through different strategies such as mRNA sequence analysis, and functional screening. In this study, a comprehensive analysis of the host transcriptome including mRNA, lncRNA, and alternative splicing was performed using human cell lines expressing dCas9-SAM and HIV-targeting msgRNAs.
resultsThe control scrambled msgRNA (LTR_Zero), and two LTR-specific msgRNAs (LTR_L and LTR_O) groups show very similar expression profiles of the whole transcriptome. Among 839 identified lncRNAs, none exhibited significantly different expression in LTR_L vs. LTR_Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were significantly decreased. Among 142,791 mRNAs, four genes were differentially expressed in LTR_L vs. LTR_Zero group. There were 21 genes significantly downregulated in LTR_O vs. either LTR_Zero or LTR_L group and one third of them are histone related. The distributions of different types of alternative splicing were very similar either within or between groups. There were no apparent changes in all the lncRNA and mRNA transcripts between the LTR_L and LTR_Zero groups.
conclusionThis is an extremely comprehensive study demonstrating the rare off-target effects of the HIV-specific dCas9-SAM system in human cells. This finding is encouraging for the safe application of dCas9-SAM technology to induce target-specific reactivation of latent HIV for an effective "shock-and-kill" strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.