ArticleMolecular therapy. Methods & clinical development2022
A combinatorial CRISPR-Cas12a attack on HIV DNA.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- 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
- Research progress on HIV-1 structural proteins and antiviral therapies.Frontiers in immunology · 2026Review
- Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control.AIDS research and treatment · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- Molecular chaperones at the host-virus interface: heat shock protein roles in HIV-1 and emerging insights for HIV-2 and dual infection.Frontiers in cellular and infection microbiology · 2025Review
- The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection.Pathogens (Basel, Switzerland) · 2024Review
- Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.Vaccines · 2024Review
- CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA.Journal of virology · 2023Article
- Killing two birds with one stone: CRISPR/Cas9 CCR5 knockout hematopoietic stem cells transplantation to treat patients with HIV infection and hematological malignancies concurrently.Clinical and experimental medicine · 2023Review
- In-house ELISA protocols for capsid p24 detection of diverse HIV isolates.Virology journal · 2023Article
- CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- A CRISPR-Cas Cure for HIV/AIDS.International journal of molecular sciences · 2023Review
- Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.Frontiers in genome editing · 2023Article
- Complete and Prolonged Inhibition of Herpes Simplex Virus Type 1 Infection In Vitro by CRISPR/Cas9 and CRISPR/CasX Systems.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
CRISPR-Cas12a is an alternative class 2 gene editing tool that may cause less off-target effects than the original Cas9 system. We have previously demonstrated that Cas12a attack with a single CRISPR RNA (crRNA) can neutralize all infectious HIV in an infected T cell line in cell culture. However, we demonstrated that HIV escapes from most crRNAs by acquisition of a mutation in the crRNA target sequence, thus providing resistance against Cas12a attack. Here, we tested the antiviral activity of seven dual crRNA combinations and analyzed the HIV proviral genomes for mutations at the target sites. We demonstrated that dual crRNA combinations exhibit more robust antiviral activity than a single crRNA attack and, more important, that the dual-crRNA therapy can prevent virus escape in long-term cultures. We confirmed the absence of any replication-competent virus in these apparently cured cultures. Surprisingly, we did not detect excision of the HIV sequences located between two Cas12a cleavage sites. Instead, we observed almost exclusively HIV inactivation by "hypermutation," that is, the introduction of indel mutations at both target sites due to the error-prone cellular DNA repair machinery.
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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.