ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 181 citations in OpenAlex.
- Advances and applications of genome-edited animal models for severe combined immunodeficiency.Zoological research · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases.Gene therapy · 2025Review
- Advancing towards HIV-1 remission: Insights and innovations in stem cell therapies.Archives of stem cell and therapy · 2024Article
- Review
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- Addressing the dark matter of gene therapy: technical and ethical barriers to clinical application.Human genetics · 2022Review
- CRISPR-Cas9-mediated gene disruption of HIV-1 co-receptors confers broad resistance to infection in human T cells and humanized mice.Molecular therapy. Methods & clinical development · 2022Article
- Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders.Frontiers in genome editing · 2022Review
- The CCR5 Gene Edited CD34Frontiers in immunology · 2022Article
- Understanding and overcoming adverse consequences of genome editing on hematopoietic stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- The Strategies and Challenges of CCR5 Gene Editing in Hematopoietic Stem and Progenitor Cells for the Treatment of HIV.Stem cell reviews and reports · 2021Review
- Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure.Frontiers in immunology · 2021Review
- Gene Editing in Pluripotent Stem Cells and Their Derived Organoids.Stem cells international · 2021Review
- Robust expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates.Blood · 2020Article
- Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.Molecular therapy. Methods & clinical development · 2020Review
- Advance genome editing technologies in the treatment of human diseases: CRISPR therapy (Review).International journal of molecular medicine · 2020Review
- Genome-edited adult stem cells: Next-generation advanced therapy medicinal products.Stem cells translational medicine · 2020Review
- Review
43 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
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5(Δ32/Δ32)) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5(Δ32/Δ32) donors, we reasoned that engineered autologous CD34(+) hematopoietic stem/progenitor cells (HSPCs) could be used for AIDS therapy. We evaluated disruption of CCR5 gene expression in HSPCs isolated from granulocyte colony-stimulating factor (CSF)-mobilized adult blood using a recombinant adenoviral vector encoding a CCR5-specific pair of zinc finger nucleases (CCR5-ZFN). Our results demonstrate that CCR5-ZFN RNA and protein expression from the adenoviral vector is enhanced by pretreatment of HSPC with protein kinase C (PKC) activators resulting in >25% CCR5 gene disruption and that activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is responsible for this activity. Importantly, using an optimized dose of PKC activator and adenoviral vector we could generate CCR5-modified HSPCs which engraft in a humanized mouse model (albeit at a reduced level) and support multilineage differentiation in vitro and in vivo. Together, these data establish the basis for improved approaches exploiting adenoviral vector delivery in the modification of HSPCs.
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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.