ArticleAIDS research and human retroviruses2018
Broad-Spectrum and Personalized Guide RNAs for CRISPR/Cas9 HIV-1 Therapeutics.
Article in AIDS research and human retroviruses, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- HIV cure: from early therapies to cutting-edge strategies.Journal of neurovirology · 2026Review
- 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
- An Update on the Application of CRISPR Technology in Clinical Practice.Molecular biotechnology · 2024Review
- Delivering CRISPR to the HIV-1 reservoirs.Frontiers in microbiology · 2024Review
- Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.Frontiers in genome editing · 2023Article
- 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
- Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection.Frontiers in cellular and infection microbiology · 2022Review
- Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line.Viruses · 2021Article
- Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.Pathogens (Basel, Switzerland) · 2021Review
- 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
- Inactivation of Latent HIV-1 Proviral DNA Using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Treatment and the Assessment of Off-Target Effects.Frontiers in 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
- Balance between Retroviral Latency and Transcription: Based on HIV Model.Pathogens (Basel, Switzerland) · 2020Review
- MultiplexedViruses · 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
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Authors and funding
17 authors.
Funding
Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system has been used to excise the HIV-1 proviral genome from latently infected cells, potentially offering a cure for HIV-infected patients. Recent studies have shown that most published HIV-1 guide RNAs (gRNAs) do not account for the diverse viral quasispecies within or among patients, which continue to diversify with time even in long-term antiretroviral therapy (ART)-suppressed patients. Given this observation, proviral genomes were deep sequenced from 23 HIV-1-infected patients in the Drexel Medicine CNS AIDS Research and Eradication Study cohort at two different visits. Based on the spectrum of integrated proviral DNA polymorphisms observed, three gRNA design strategies were explored: based on the patient's own HIV-1 sequences (personalized), based on consensus sequences from a large sample of patients [broad-spectrum (BS)], or a combination of both approaches. Using a bioinformatic algorithm, the personalized gRNA design was predicted to cut 46 of 48 patient samples at 90% efficiency, whereas the top 4 BS gRNAs (BS4) were predicted to excise provirus from 44 of 48 patient samples with 90% efficiency. Using a mixed design with the top three BS gRNAs plus one personalized gRNA (BS3 + PS1) resulted in predicted excision of provirus from 45 of 48 patient samples with 90% efficiency. In summary, these studies used an algorithmic design strategy to identify potential BS gRNAs to target a spectrum of HIV-1 long teriminal repeat (LTR) quasispecies for use with a small HIV-1-infected population. This approach should advance CRISPR/Cas9 excision technology taking into account the extensive molecular heterogeneity of HIV-1 that persists in situ after prolonged ART.
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