ArticleThe Journal of clinical investigation2003
In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 85 citations in OpenAlex.
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- Enhancing cellular immunotherapies in cancer by engineering selective therapeutic resistance.Nature reviews. Cancer · 2024Review
- In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy.Journal of cellular physiology · 2021Article
- Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018Review
- Clinical Applications of Genome Editing to HIV Cure.AIDS patient care and STDs · 2016Article
- Review
- Towards in vivo amplification: Overcoming hurdles in the use of hematopoietic stem cells in transplantation and gene therapy.World journal of stem cells · 2015Review
- PDGFB-based stem cell gene therapy increases bone strength in the mouse.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- MGMT enrichment and second gene co-expression in hematopoietic progenitor cells using separate or dual-gene lentiviral vectors.Virus research · 2015Article
- S/MAR sequence confers long-term mitotic stability on non-integrating lentiviral vector episomes without selection.Nucleic acids research · 2014Article
- Efficiency and safety of O⁶-methylguanine DNA methyltransferase (MGMT(P140K))-mediated in vivo selection in a humanized mouse model.Human gene therapy · 2014Article
- Genetic modification of mouse bone marrow by lentiviral vector-mediated delivery of hypoxanthine-Guanine phosphoribosyltransferase short hairpin RNA confers chemoprotection against 6-thioguanine cytotoxicity.Transplantation proceedings · 2013Article
- Efficient in vivo regulation of cytidine deaminase expression in the haematopoietic system using a doxycycline-inducible lentiviral vector system.Gene therapy · 2013Article
- Knockdown of HPRT for selection of genetically modified human hematopoietic progenitor cells.PloS one · 2013Article
- Chemoselection of allogeneic HSC after murine neonatal transplantation without myeloablation or post-transplant immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Treatment of a solid tumor using engineered drug-resistant immunocompetent cells and cytotoxic chemotherapy.Human gene therapy · 2012Article
- Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo.ISRN hematology · 2012Article
- Impact of temozolomide on immune response during malignant glioma chemotherapy.Clinical & developmental immunology · 2012Review
- Imaging stem cell-derived persistent foci after in vivo selection of lentiviral MGMT-P140K transduced murine bone marrow cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Ex vivo gene transfer and correction for cell-based therapies.Nature reviews. Genetics · 2011Review
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Infusion of transduced hematopoietic stem cells into nonmyeloablated hosts results in ineffective in vivo levels of transduced cells. To increase the proportion of transduced cells in vivo, selection based on P140K O6-methylguanine-DNA-methyltransferase (MGMT[P140K]) gene transduction and O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea (BG/BCNU) treatment has been devised. In this study, we transduced human NOD/SCID repopulating cells (SRCs) with MGMT(P140K) using a lentiviral vector and infused them into BG/BCNU-conditioned NOD/SCID mice before rounds of BG/BCNU treatment as a model for in vivo selection. Engraftment was not observed until the second round of BG/BCNU treatment, at which time human cells emerged to compose up to 20% of the bone marrow. Furthermore, 99% of human CFCs derived from NOD/SCID mice were positive for provirus as measured by PCR, compared with 35% before transplant and 11% in untreated irradiation-preconditioned mice, demonstrating selection. Bone marrow showed BG-resistant O6-alkylguanine-DNA-alkyltransferase (AGT) activity, and CFUs were stained intensely for AGT protein, indicating high transgene expression. Real-time PCR estimates of the number of proviral insertions in individual CFUs ranged from 3 to 22. Selection resulted in expansion of one or more SRC clones containing similar numbers of proviral copies per mouse. To our knowledge, these results provide the first evidence of potent in vivo selection of MGMT(P140K) lentivirus-transduced human SRCs following BG/BCNU treatment.
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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.