ArticleScientific reports2019
Novel gRNA design pipeline to develop broad-spectrum CRISPR/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Impact of chromatin on HIV-1 latency: a multi-dimensional perspective.Epigenetics & chromatin · 2025Review
- Delivering CRISPR to the HIV-1 reservoirs.Frontiers in microbiology · 2024Review
- Editorial: Prevention of viral diseases by gene targeting.Frontiers in genome editing · 2024Article
- Assessment of anti-HIV-1 guide RNA efficacy in cells containing the viral target sequence, corresponding gRNA, and CRISPR/Cas9.Frontiers in genome editing · 2023Article
- Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.Frontiers in genome editing · 2023Article
- The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy.Journal of advanced research · 2022Review
- HIV-1 Reservoir Persistence and Decay: Implications for Cure Strategies.Current HIV/AIDS reports · 2022Review
- Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line.Viruses · 2021Article
- CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination.EBioMedicine · 2021Article
- HIV-1 cure strategies: why CRISPR?Expert opinion on biological therapy · 2021Review
- Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.Frontiers in immunology · 2021Review
- Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy.Frontiers in cellular and infection microbiology · 2021Article
- Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR/Cas9 in HIV-1 Therapy.Frontiers in genome editing · 2021Review
- Analysis of CRISPR/Cas9 Guide RNA Efficiency and Specificity Against Genetically Diverse HIV-1 Isolates.AIDS research and human retroviruses · 2020Article
- Safe CRISPR-Cas9 Inhibition of HIV-1 with High Specificity and Broad-Spectrum Activity by Targeting LTR NF-κB Binding Sites.Molecular therapy. Nucleic acids · 2020Article
- CRISPR-Cas9 Dual-gRNA Attack Causes Mutation, Excision and Inversion of the HIV-1 Proviral DNA.Viruses · 2020Article
- Pathways towards human immunodeficiency virus elimination.EBioMedicine · 2020Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
The CRISPR/Cas9 system has been proposed as a cure strategy for HIV. However, few published guide RNAs (gRNAs) are predicted to cleave the majority of HIV-1 viral quasispecies (vQS) observed within and among patients. We report the design of a novel pipeline to identify gRNAs that target HIV across a large number of infected individuals. Next generation sequencing (NGS) of LTRs from 269 HIV-1-infected samples in the Drexel CARES Cohort was used to select gRNAs with predicted broad-spectrum activity. In silico, D-LTR-P4-227913 (package of the top 4 gRNAs) accounted for all detectable genetic variation within the vQS of the 269 samples and the Los Alamos National Laboratory HIV database. In silico secondary structure analyses from NGS indicated extensive TAR stem-loop malformations predicted to inactivate proviral transcription, which was confirmed by reduced viral gene expression in TZM-bl or P4R5 cells. Similarly, a high sensitivity in vitro CRISPR/Cas9 cleavage assay showed that the top-ranked gRNA was the most effective at cleaving patient-derived HIV-1 LTRs from five patients. Furthermore, the D-LTR-P4-227913 was predicted to cleave a median of 96.1% of patient-derived sequences from other HIV subtypes. These results demonstrate that the gRNAs possess broad-spectrum cutting activity and could contribute to an HIV cure.
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