ArticleScience translational medicine2015
Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
158 citing papers in PubMed, 227 citations in OpenAlex.
- Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL.Nature · 2022Trial
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Manufacturing and electrostatic surface optimization of CAR-T cells improve therapeutic efficacy in liver malignancies.Hepatology communications · 2026Article
- A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.Journal of hematology & oncology · 2026Article
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- High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion.Nature communications · 2026Article
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- Chimeric antigen receptor T‑cell therapy in chronic viral infections: a review.Journal of translational medicine · 2026Review
- Viral vector-free generation of orthogonal IL-2-responsive CAR T cells through gene editing of IL-2 and its receptor.Blood immunology & cellular therapy · 2025Article
- Review
- Miniaturized scalable arrayed CRISPR screening in primary cells enables discovery at the single donor resolution.Scientific reports · 2025Article
- Targeting human plasma cells using regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Genome engineering with Cas9 and AAV repair templates, successes and pitfalls.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- In vivo tracking of ex-vivo-generatedMolecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Structural basis for nuclear import of adeno-associated virus serotype 6 capsid protein.Journal of virology · 2025Article
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- Cas9-induced targeted integration of large DNA payloads in primary human T cells via homology-mediated end-joining DNA repair.Nature biomedical engineering · 2024Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Genetic mutations or engineered nucleases that disrupt the HIV co-receptor CCR5 block HIV infection of CD4(+) T cells. These findings have motivated the engineering of CCR5-specific nucleases for application as HIV therapies. The efficacy of this approach relies on efficient biallelic disruption of CCR5, and the ability to efficiently target sequences that confer HIV resistance to the CCR5 locus has the potential to further improve clinical outcomes. We used RNA-based nuclease expression paired with adeno-associated virus (AAV)-mediated delivery of a CCR5-targeting donor template to achieve highly efficient targeted recombination in primary human T cells. This method consistently achieved 8 to 60% rates of homology-directed recombination into the CCR5 locus in T cells, with over 80% of cells modified with an MND-GFP expression cassette exhibiting biallelic modification. MND-GFP-modified T cells maintained a diverse repertoire and engrafted in immune-deficient mice as efficiently as unmodified cells. Using this method, we integrated sequences coding chimeric antigen receptors (CARs) into the CCR5 locus, and the resulting targeted CAR T cells exhibited antitumor or anti-HIV activity. Alternatively, we introduced the C46 HIV fusion inhibitor, generating T cell populations with high rates of biallelic CCR5 disruption paired with potential protection from HIV with CXCR4 co-receptor tropism. Finally, this protocol was applied to adult human mobilized CD34(+) cells, resulting in 15 to 20% homologous gene targeting. Our results demonstrate that high-efficiency targeted integration is feasible in primary human hematopoietic cells and highlight the potential of gene editing to engineer T cell products with myriad functional properties.
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Registered trials
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.