ArticleViruses2019
The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape.
Article in Viruses, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 43 citations in OpenAlex.
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Combination treatment with synthetic gRNA/Cas12a and gRNA/Cas9 ribonucleoproteins disrupts HIV replication and expression.iScience · 2026Article
- Elucidating the kinetics of CRISPR-SaCas9 action to obtain effective HIV DNA excision with two gRNAs.Nucleic acids research · 2026Article
- CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025Review
- Review
- CRISPR-Cas systems: A revolution in genome editing and its diverse applications.Journal of biomed research · 2024Article
- CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Article
- A CRISPR-Cas Cure for HIV/AIDS.International journal of molecular sciences · 2023Review
- 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
- Polyvalent guide RNAs for CRISPR antivirals.iScience · 2022Article
- Article
- Guide RNAs containing universal bases enable Cas9/Cas12a recognition of polymorphic sequences.Nature communications · 2022Article
- 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 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats.Journal of virology · 2021Article
- CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination.EBioMedicine · 2021Article
- HIV-1 cure strategies: why CRISPR?Expert opinion on biological therapy · 2021Review
- Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR/Cas9 in HIV-1 Therapy.Frontiers in genome editing · 2021Review
- Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is widely explored for sequence-specific attack on HIV-1 proviral DNA. We recently identified dual-guide RNA (dual-gRNA) combinations that can block HIV-1 replication permanently in infected cell cultures and prevent viral escape. Although the gRNAs were designed to target highly conserved viral sequences, their efficacy may be challenged by high genetic variation in the HIV-1 genome. We therefore evaluated the breadth of these dual-gRNA combinations against distinct HIV-1 isolates, including several subtypes. Replication of nearly all virus isolates could be prevented by at least one gRNA combination, which caused inactivation of the proviral genomes and the gradual loss of replication-competent virus over time. The dual-gRNA efficacy was not affected by most single nucleotide (nt) mismatches between gRNA and the viral target. However, 1-nt mismatches at the Cas9 cleavage site and two mismatches anywhere in the viral target sequence significantly reduced the inhibitory effect. Accordingly, sequence analysis of viruses upon breakthrough replication revealed the acquisition of escape mutations in perfectly matching and most 1-nt mismatching targets, but not in targets with a mismatch at the Cas9 cleavage site or with two mismatches. These results demonstrate that combinatorial CRISPR-Cas9 treatment can cure T cells infected by distinct HIV-1 isolates, but even minor sequence variation in conserved viral target sites can affect the efficacy of this strategy. Successful cure attempts against isolates with divergent target sequences may therefore require adaptation of the gRNAs.
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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.