ArticleThe Journal of clinical investigation2010
Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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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
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Persistence of CRISPR/Cas9 gene edited hematopoietic stem cells following transplantation: A systematic review and meta-analysis of preclinical studies.Stem cells translational medicine · 2021Pooled it
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- Novel and emerging therapeutic strategies for clonal hematopoiesis.Haematologica · 2026Review
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- Multiplex base editing to protect from CD33 directed drugs for immune and gene therapy.Nature communications · 2025Article
- Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques.Blood advances · 2025Article
- CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1.Scientific reports · 2024Article
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
- In vivo selection of anti-HIV-1 gene-modified human hematopoietic stem/progenitor cells to enhance engraftment and HIV-1 inhibition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Efficient long-term multilineage engraftment of CD33-edited hematopoietic stem/progenitor cells in nonhuman primates.Molecular therapy. Methods & clinical development · 2023Article
- Potent dual block to HIV-1 infection using lentiviral vectors expressing fusion inhibitor peptide mC46- and Vif-resistant APOBEC3G.Molecular therapy. Nucleic acids · 2023Article
- Enrichment strategies to enhance genome editing.Journal of biomedical science · 2023Review
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- Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.JCI insight · 2022Article
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- Safe and efficientMolecular therapy. Methods & clinical development · 2022Article
23 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
6 authors at 1 institution in 1 country.
Funding
Abstract
HSC transplantation using genetically modified autologous cells is a promising therapeutic strategy for various genetic diseases, cancer, and HIV. However, for many of these conditions, the current efficiency of gene transfer to HSCs is not sufficient for clinical use. The ability to increase the percentage of gene-modified cells following transplantation is critical to overcoming this obstacle. In vivo selection with mutant methylguanine methyltransferase (MGMTP140K) has been proposed to overcome low gene transfer efficiency to HSCs. Previous studies have shown efficient in vivo selection in mice and dogs but only transient selection in primates. Here, we report efficient and stable MGMTP140K-mediated multilineage selection in both macaque and baboon nonhuman primate models. Treatment consisting of both O6-benzylguanine (O6BG) and N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU) stably increased the percentage of transgene-expressing cells from a range of initial levels of engrafted genetically modified cells, with the longest follow-up after drug treatment occurring over 2.2 years. Drug treatment was well tolerated, and selection occurred in myeloid, lymphoid, and erythroid cells as well as platelets. Retrovirus integration site analysis before and after drug treatments confirmed the presence of multiple clones. These nonhuman primate studies closely model a clinical setting and should have broad applications for HSC gene therapy targeting human diseases of malignant, genetic, and infectious nature, including HIV.
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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.