Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection
Open accessAbstract
Significance: Patients homozygous for the C-C chemokine receptor type 5 (CCR5) gene with 32-bp deletions (Δ32) are resistant to HIV infection. Using the piggyBac technology plus transcription activator-like effector nucleases or clustered regularly interspaced short palindromic repeats-Cas9, the authors report, to our knowledge, for the first time in induced pluripotent stem cells (iPSCs) the efficient and seamless derivation of a homozygous CCR5Δ32 mutation, exactly mimicking the natural mutation. Monocytes and macrophages differentiated from these mutated iPSCs in vitro are resistant to HIV infection. This approach can be applied in the future toward the functional cure of HIV infection. The findings are also of great interest to researchers in many fields who wish to correct or introduce mutations in specific genes.
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Mutation in CCR5 leading to cell-resistance to HIV-1 infection was achieved in iPSCs with CRISPR-Cas9.
“For example, mutation in CCR5 (CC chemokine receptor 5) gene that leads to cell-resistance to HIV-1 infection was achieved in iPSCs with CRISPR-Cas9.37”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [37]
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- Authors
- Ye, L., Wang, J., Beyer, A. I., Teque, F., Cradick, T. J., Qi, Z., Chang, J. C., Bao, G., Muench, M. O., Yu, J., Levy, J. A., & Kan, Y. W.
- Affiliations
- Department of Medicine and Institute for Human Genetics,
- Blood Systems Research Institute (US)
- University of California, San Francisco (US)
- Georgia Institute of Technology (US)
- Department of Laboratory Medicine, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-06-09
- Volume
- 111
- Issue
- 26
- Pages
- 9591-9596
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4084478
- OpenAlex
- W2053763799
- Cited by
- 320
- References
- 36
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 31 · 2021: 19 · 2020: 22 · 2019: 24 · 2018: 36 · 2017: 38 · 2016: 49 · 2015: 45 · 2014: 15
- FWCI
- 20.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Allergy and Infectious Diseases (R56AI102825, AI 102825, R01AI102825)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK088760)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- CCR5 delta32 mutation, induced pluripotent stem cells, HIV-1 resistance, genome editing, TALEN, CRISPR/Cas9, piggyBac transposon, monocytes/macrophages, chemokine receptors
- MeSH terms
- Cell Differentiation, Cells, Cultured, Deoxyribonucleases, Fluorescent Antibody Technique, Genetic Engineering, Genetic Vectors, Humans, Macrophages, Monocytes, Blotting, Southern, HIV Infections, Mutagenesis, Sequence Deletion, DNA Primers, Receptors, CCR5, Transposases, Induced Pluripotent Stem Cells, Disease Resistance, Clustered Regularly Interspaced Short Palindromic Repeats
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