ArticleMolecular therapy. Nucleic acids2015
CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 153 citations in OpenAlex.
- CRISPR Applications in HIV Management - Prevention, Diagnosis, Monitoring and Treatment.Current HIV/AIDS reports · 2026Review
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Searching for a HIV-1 Cure.Theranostics · 2026Review
- Beyond monotherapy: Combination therapies for HIV-1 cure through joint application of neutralizing antibodies, genome editing, and reservoir management.Infectious medicine · 2025Review
- Moyamoya disease: epidemiology, clinical features, pathogenesis, diagnosis and therapeutic interventions.Molecular biomedicine · 2025Review
- CRISPR-Cas technologies: Emerging tools from research to clinical application.Journal of microbiology (Seoul, Korea) · 2025Review
- Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target.Inflammopharmacology · 2025Review
- Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease.Nature reviews. Immunology · 2025Review
- Synergy between pluripotent stem cell-derived macrophages and self-renewing macrophages: Envisioning a promising avenue for the modelling and cell therapy of infectious diseases.Cell proliferation · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- CRISPR/Cas9-mediated genome editing technique to control fall armyworm (Physiology and molecular biology of plants : an international journal of functional plant biology · 2024Review
- Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes.iScience · 2023Article
- Antiretrovirals to CCR5 CRISPR/Cas9 gene editing - A paradigm shift chasing an HIV cure.Clinical immunology (Orlando, Fla.) · 2023Review
- A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications.Molecular therapy. Methods & clinical development · 2023Article
- Review
- CRISPR/Cas System Toward the Development of Next-Generation Recombinant Vaccines: Current Scenario and Future Prospects.Arabian journal for science and engineering · 2023Review
- CRISPR/Cas9 genome editing to create nonhuman primate models for studying stem cell therapies for HIV infection.Retrovirology · 2022Review
- Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation.Pathogens (Basel, Switzerland) · 2022Review
- Closing the Door with CRISPR: Genome Editing of CCR5 and CXCR4 as a Potential Curative Solution for HIV.Biotech (Basel (Switzerland)) · 2022Review
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.
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Registered trials
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