ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Ex vivo expansion of retrovirally transduced primate CD34+ cells results in overrepresentation of clones with MDS1/EVI1 insertion sites in the myeloid lineage after transplantation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Comparative engraftment and clonality of macaque HSPCs expanded on human umbilical vein endothelial cells versus non-expanded cells.Molecular therapy. Methods & clinical development · 2021Article
- Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Review
- A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance.Molecular therapy. Methods & clinical development · 2016Article
- Clonal Dominance With Retroviral Vector Insertions Near the ANGPT1 and ANGPT2 Genes in a Human Xenotransplant Mouse Model.Molecular therapy. Nucleic acids · 2014Article
- Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.Journal of stem cell research & therapy · 2013Article
- Long-term follow-up of foamy viral vector-mediated gene therapy for canine leukocyte adhesion deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.Leukemia · 2013Article
- Transduction of human CD34+ repopulating cells with a self-inactivating lentiviral vector for SCID-X1 produced at clinical scale by a stable cell line.Human gene therapy methods · 2012Article
- Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.Human gene therapy · 2012Article
- Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity.Frontiers of medicine · 2011Review
- Genotoxicity of retroviral hematopoietic stem cell gene therapy.Expert opinion on biological therapy · 2011Review
- Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chain Mice.Bone marrow research · 2011Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Activation of proto-oncogenes by retroviral insertion is an important issue delaying clinical development of gene therapy. We have reported the nonrandom persistence of hematopoietic clones with vector insertions within the MDS1/EVI1 locus following transplantation of rhesus macaques. We now ask whether prolonged culture of transduced CD34(+) cells before transplantation selects for clones with insertions in the MDS1/EVI11 or other proto-oncogene loci. CD34(+) cells were transduced with standard retroviral vectors for 4 days and then continued in culture for an additional 6 days before transplantation. A 15% of insertions identified in granulocytes 6 months post-transplant were in MDS1/EVI11, significantly increased compared to the frequency in animals transplanted with cells immediately following transduction. MDS1/EVI1 clones became more dominant over time post-transplantation in one animal that was followed long term, accompanied by an increased overall copy number of vector-containing granulocytes, with one MDS1/EVI1 clone eventually accounting for 100% of transduced granulocytes and marrow colony-forming unit (CFU). This vector insertion increased the expression of Evi1 mRNA. There was no overrepresentation of MDS1/EVI1 insertions contributing to lymphoid lineages. Strategies involving prolonged ex vivo expansion of transduced cells may increase the risk of genotoxicity.
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