ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Cell cycle status of CD34(+) hemopoietic stem cells determines lentiviral integration in actively transcribed and development-related genes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- DNA contamination within recombinant adeno-associated virus preparations correlates with decreased CD34Molecular therapy. Methods & clinical development · 2024Article
- Mesenchymal stromal cells with chimaeric antigen receptors for enhanced immunosuppression.Nature biomedical engineering · 2024Article
- In search of an ideal template for therapeutic genome editing: A review of current developments for structure optimization.Frontiers in genome editing · 2023Review
- In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions.Nature communications · 2022Article
- The Promise and the Hope of Gene Therapy.Frontiers in genome editing · 2021Review
- Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent.Blood advances · 2017Article
- Prolonged Integration Site Selection of a Lentiviral Vector in the Genome of Human Keratinocytes.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene therapy utilizing lentiviral-vectors (LVs) is postulated as a dynamic therapeutic alternative for monogenic diseases. However, retroviral gene transfer may cause insertional mutagenesis. Although, such risks had been originally estimated as extremely low, several reports of leukemias or clonal dominance, have led to a re-evaluation of the mechanisms operating in insertional mutagenesis. Therefore, unraveling the mechanism of retroviral integration is mandatory toward safer gene therapy applications. In the present study, we undertook an experimental approach which enabled direct correlation of the cell cycle stage of the target cell with the integration profile of LVs. CD34(+) cells arrested at different stages of cell cycle, were transduced with a GFP-LV. LAM-PCR was employed for integration site detection, followed by microarray analysis to correlate transcribed genes with integration sites. The results indicate that ~10% of integration events occurred in actively transcribed genes and that the cell cycle stage of target cells affects integration pattern. Specifically, use of thymine promoted a safer profile, since it significantly reduced integration within cell cycle-related genes, while we observed increased possibility for integration into genes related to development, and decreased possibility for integration within cell cycle and cancer-related genes, when transduction occurs during mitosis.
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