ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Extensive methylation of promoter sequences silences lentiviral transgene expression during stem cell differentiation in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 108 citations in OpenAlex.
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- Tet Transgene Activation is Disrupted in Lipogenic Triple Negative Breast Cancer Cells.ACS synthetic biology · 2025Article
- PTEN Loss Shapes Macrophage Dynamics in High-Grade Serous Ovarian Carcinoma.Cancer research · 2024Article
- Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells.Development (Cambridge, England) · 2024Article
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- MAGIK: A rapid and efficient method to create lineage-specific reporters in human pluripotent stem cells.Stem cell reports · 2024Article
- A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors.Genes · 2024Article
- Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium.Cellular and molecular life sciences : CMLS · 2024Article
- Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.Scientific reports · 2024Article
- Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer.Cancers · 2024Article
- The genetically modified human foreskin fibroblast cell line (YhFF#8) stably expressingInternational journal of reproductive biomedicine · 2024Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells.Nature communications · 2023Article
- Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids.bioRxiv : the preprint server for biology · 2023Article
- Stable expression of large transgenes via the knock-in of an integrase-deficient lentivirus.Nature biomedical engineering · 2023Article
- Generation of Induced Pluripotent Stem Cells from Lymphoblastoid Cell Lines by Electroporation of Episomal Vectors.International journal of stem cells · 2023Article
14 more citing papers are in PubMed but not listed here.
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14 authors at 4 institutions in 2 countries.
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Abstract
Lentiviral vectors (LV) are widely used to stably transfer genes into target cells investigating or treating gene functions. In addition, gene transfer into early murine embryos may be improved to efficiently generate transgenic mice. We applied lentiviral gene transfer to generate a mouse model transgenic for SET binding protein-1 (Setbp1) and enhanced green fluorescent protein (eGFP). Neither transgenic founders nor their vector-positive offspring transcribed or expressed the transgenes. Bisulfite sequencing of the internal spleen focus-forming virus (SFFV) promoter demonstrated extensive methylation of all analyzed CpGs in the transgenic mice. To analyze the impact of Setbp1 on epigenetic silencing, embryonic stem cells (ESC) were differentiated into cardiomyocytes (CM) in vitro. In contrast to human promoters in LV, virally derived promoter sequences were strongly methylated during differentiation, independent of the transgene. Moreover, the commonly used SFFV promoter (SFFVp) was highly methylated with remarkable strength and frequency during hematopoietic differentiation in vivo in LV but less in γ-retroviral (γ-RV) backbones. In summary, we conclude that LV using an internal SFFVp are not suitable to generate transgenic mice or perform constitutive expression studies in differentiating cells. Choosing the appropriate promoter is also crucial to allow stable transgene expression in clinical gene therapy.
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