ArticleScientific reports2016
Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 102 citations in OpenAlex.
- CD4-directed nanoblades enable selective genome editing in CD4EMBO molecular medicine · 2026Article
- Combination treatment with synthetic gRNA/Cas12a and gRNA/Cas9 ribonucleoproteins disrupts HIV replication and expression.iScience · 2026Article
- Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death.Nature communications · 2025Article
- Excision of HIV-1 Provirus in Human Primary Cells with Nanocapsuled TALEN Proteins.ACS applied bio materials · 2025Article
- CRISPR-Cas9-mediated genome editing delivered by a single AAV9 vector inhibits HSV-1 reactivation in a latent rabbit keratitis model.Molecular therapy. Methods & clinical development · 2024Article
- High-resolution Inference of Multiplexed Anti-HIV Gene Editing using Single-Cell Targeted DNA Sequencing.bioRxiv : the preprint server for biology · 2024Article
- CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA.Journal of virology · 2023Article
- Potency of CRISPR-Cas Antifungals Is Enhanced by Cotargeting DNA Repair and Growth Regulatory Machinery at the Genetic Level.ACS infectious diseases · 2023Article
- Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The Effect of Treatment-Associated Mutations on HIV Replication and Transmission Cycles.Viruses · 2022Review
- Article
- Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Article
- Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection.Frontiers in cellular and infection microbiology · 2022Review
- The State-of-the-Art of Gene Editing and its Application to Viral Infections and Diseases Including COVID-19.Frontiers in cellular and infection microbiology · 2022Review
- Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Editing out HIV: application of gene editing technology to achieve functional cure.Retrovirology · 2021Review
- 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
- Multiplexed Simian Immunodeficiency Virus-Specific Paired RNA-Guided Cas9 Nickases Inactivate Proviral DNA.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance.
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Registered trials
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