ArticleGene therapy2017
Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.
Article in Gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Silencing of optogenetic and chemogenetic transgenes in human iPSCs involves promoter methylation and methylation-independent mechanisms.Epigenetics · 2026Article
- Minimal CBX3-Derived UCOE Confers Long-Term Resistance to Transgene Silencing in Human iPSCs During Neuronal Differentiation.International journal of molecular sciences · 2026Article
- Ex vivo long-term expansion of human hematopoietic stem and progenitor cells as a tool for modeling vector integration sites and clonality.Journal of translational medicine · 2026Article
- XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.Stem cell reports · 2025Article
- EF1α, rather than CMV promoter, is suitable for luciferase tag expression in target cells forMolecular therapy. Methods & clinical development · 2025Article
- Optimized pipeline and designer cells for synthetic-biology-based high-throughput screening of viral protease inhibitors.Cell reports methods · 2025Article
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation.Nucleic acids research · 2025Article
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- Human stem cell-specific epigenetic signatures control transgene expression.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Article
- Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting.Viruses · 2024Article
- The characteristics of excitatory lineage differentiation and the developmental conservation in Reeler neocortex.Cell proliferation · 2024Article
- Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer.Frontiers in immunology · 2024Article
- Inflammation-inducible promoters to overexpress immune inhibitory factors by MSCs.Stem cell research & therapy · 2023Article
- Development of anMolecular therapy. Methods & clinical development · 2023Article
- Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies.Biomarker research · 2023Review
- OPTO-BLUE: An Integrated Bidirectional Optogenetic Lentiviral Platform for Controlled Light-Induced Gene Expression.International journal of molecular sciences · 2023Article
- [Research progress of induced pluripotent stem cells in promoting wound healing of diabetic foot ulcers].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- Viruses as tools in gene therapy, vaccine development, and cancer treatment.Archives of virology · 2022Review
- AAV-p40 Bioengineering Platform for Variant Selection Based on Transgene Expression.Human gene therapy · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes. Lentiviral vectors (LV) pseudotyped with vesicular stomatitis virus glycoprotein were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. The elongation factor 1α short (EFS) promoter mediated the most robust expression, whereas expression levels were lower from the potent but more silencing-prone spleen focus forming virus (SFFV) promoter. Both full-length (A2UCOE) and minimal (CBX3) UCOE juxtaposed to two physiological and one viral promoter reduced transgene silencing with equal efficiency. However, a promoter-specific decline in expression levels was not entirely prevented. Upon differentiation of transgene-positive iPSC into endothelial cells, A2UCOE.EFS and CBX3.EFS vectors maintained highest transgene expression in a larger fraction of cells as compared with all other constructs tested here. The function of UCOE diminished, but did not fully counteract, vector silencing and possibilities for improvements remain. Nevertheless, the CBX3.EFS in a LV background exhibited the most promising promoter and vector configuration for both high titer production and long-term genetic modification of human iPSC and their progeny.
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