ArticleHuman gene therapy2014
Dissecting the mechanism of histone deacetylase inhibitors to enhance the activity of zinc finger nucleases delivered by integrase-defective lentiviral vectors.
Article in Human gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs.Science China. Life sciences · 2021Article
- Integrase-Defective Lentiviral Vector Is an Efficient Vaccine Platform for Cancer Immunotherapy.Viruses · 2021Article
- Enhanced Generation of Induced Cardiomyocytes Using a Small-Molecule Cocktail to Overcome Barriers to Cardiac Cellular Reprogramming.Journal of the American Heart Association · 2020Article
- Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing.Nucleic acids research · 2020Article
- Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features.Stem cells international · 2020Article
- The IS2 Element Improves Transcription Efficiency of Integration-Deficient Lentiviral Vector Episomes.Molecular therapy. Nucleic acids · 2018Article
- Prostaglandin EMolecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Integration-defective lentiviral vector mediates efficient gene editing through homology-directed repair in human embryonic stem cells.Nucleic acids research · 2017Article
- Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear Entry.Cell host & microbe · 2016Article
- A genome editing primer for the hematologist.Blood · 2016Review
- Engineered Viruses as Genome Editing Devices.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Integrase-defective lentiviral vectors (IDLVs) have been of limited success in the delivery of zinc finger nucleases (ZFNs) to human cells, due to low expression. A reason for reduced gene expression has been proposed to involve the epigenetic silencing of vector genomes, carried out primarily by histone deacetylases (HDACs). In this study, we tested valproic acid (VPA), a known HDAC inhibitor (HDACi), for its ability to increase transgene expression from IDLVs, especially in the context of ZFN delivery. Using ZFNs targeting the human adenosine deaminase (ADA) gene in K562 cells, we demonstrated that treatment with VPA enhanced ZFN expression by up to 3-fold, resulting in improved allelic disruption at the ADA locus. Furthermore, three other U.S. Food and Drug Administration-approved HDACis (vorinostat, givinostat, and trichostatin-A) exhibited a similar effect on the activity of ZFN-IDLVs in K562 cells. In primary human CD34(+) cells, VPA- and vorinostat-treated cells showed higher levels of expression of both green fluorescent protein (GFP) as well as ZFNs from IDLVs. A major mechanism for the effects of HDAC inhibitors on improving expression was from their modulation of the cell cycle, and the influence of heterochromatinization was determined to be a lesser contributing factor.
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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.