ArticleBlood2009
Amelioration of murine beta-thalassemia through drug selection of hematopoietic stem cells transduced with a lentiviral vector encoding both gamma-globin and the MGMT drug-resistance gene.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Enhanced expression of the human Survival motor neuron 1 gene from a codon-optimised cDNA transgene in vitro and in vivo.Gene therapy · 2023Article
- In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy.Journal of cellular physiology · 2021Article
- Article
- In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia.The Journal of clinical investigation · 2019Article
- Endothelial cell α-globin and its molecular chaperone α-hemoglobin-stabilizing protein regulate arteriolar contractility.The Journal of clinical investigation · 2018Article
- Lentiviral Transfer of γ-Globin with Fusion Gene NUP98-HOXA10HD Expands Hematopoietic Stem Cells and Ameliorates Murine β-Thalassemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- Towards in vivo amplification: Overcoming hurdles in the use of hematopoietic stem cells in transplantation and gene therapy.World journal of stem cells · 2015Review
- Recent trends in the gene therapy of β-thalassemia.Journal of blood medicine · 2015Review
- In vivo enrichment of genetically manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infection.Journal of thrombosis and haemostasis : JTH · 2014Article
- Gene therapy for hemoglobinopathies: the state of the field and the future.Hematology/oncology clinics of North America · 2014Review
- Efficiency and safety of O⁶-methylguanine DNA methyltransferase (MGMT(P140K))-mediated in vivo selection in a humanized mouse model.Human gene therapy · 2014Article
- MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain.Gene therapy · 2014Article
- Hematopoietic stem cell gene therapy:assessing the relevance of preclinical models.Seminars in hematology · 2013Review
- 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
- Development of gene therapy for thalassemia.Cold Spring Harbor perspectives in medicine · 2012Review
- Chemoprotection in brain tumor patients: another success for stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Recent advances in gene therapy for thalassemia.Journal of pharmacy & bioallied sciences · 2012Article
- Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function.Gene therapy · 2012Review
- Cell Membrane-associated heparan sulfate is a receptor for prototype foamy virus in human, monkey, and rodent cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
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
Correction of murine models of beta-thalassemia has been achieved through high-level globin lentiviral vector gene transfer into mouse hematopoietic stem cells (HSCs). However, transduction of human HSCs is less robust and may be inadequate to achieve therapeutic levels of genetically modified erythroid cells. We therefore developed a double gene lentiviral vector encoding both human gamma-globin under the transcriptional control of erythroid regulatory elements and methylguanine methyltransferase (MGMT), driven by a constitutive cellular promoter. MGMT expression provides cellular resistance to alkylator drugs, which can be administered to kill residual untransduced, diseased HSCs, whereas transduced cells are protected. Mice transplanted with beta-thalassemic HSCs transduced with a gamma-globin/MGMT vector initially had subtherapeutic levels of red cells expressing gamma-globin. To enrich gamma-globin-expressing cells, transplanted mice were treated with the alkylator agent 1,3-bis-chloroethyl-1-nitrosourea. This resulted in significant increases in the number of gamma-globin-expressing red cells and the amount of fetal hemoglobin, leading to resolution of anemia. Selection of transduced HSCs was also obtained when cells were drug-treated before transplantation. Mice that received these cells demonstrated reconstitution with therapeutic levels of gamma-globin-expressing cells. These data suggest that MGMT-based drug selection holds promise as a modality to improve gene therapy for beta-thalassemia.
Indexed as
Identifiers
What OpenQuestion holds
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.