ArticleVirology journal2006
Inhibition of histone deacetylation in 293GPG packaging cell line improves the production of self-inactivating MLV-derived retroviral vectors.
Article in Virology journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Enhancing titers of therapeutic lentiviral vectors using PKC agonists.Molecular therapy. Methods & clinical development · 2025Article
- Improved Manufacturing Methods of Extracellular Vesicles Pseudotyped with the Vesicular Stomatitis Virus Glycoprotein.Molecular biotechnology · 2024Article
- Optimizing and developing a scalable, chemically defined, animal component-free lentiviral vector production process in a fixed-bed bioreactor.Molecular therapy. Methods & clinical development · 2023Article
- Article
- Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells.Medical microbiology and immunology · 2020Article
- Development of a laboratory scalable process for enhancing lentivirus production by transient transfection of HEK293 adherent cultures.Gene therapy · 2019Article
- LentiPro26: novel stable cell lines for constitutive lentiviral vector production.Scientific reports · 2018Article
- A Protocol for the Production of Integrase-deficient Lentiviral Vectors for CRISPR/Cas9-mediated Gene Knockout in Dividing Cells.Journal of visualized experiments : JoVE · 2017Article
- Production of lentiviral vectors.Molecular therapy. Methods & clinical development · 2016Review
- Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells.Experimental cell research · 2015Article
- Evaluation of residual promoter activity in γ-retroviral self-inactivating (SIN) vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Human embryonic stem cells which express hrGFP in the undifferentiated state and during dopaminergic differentiation.Restorative neurology and neuroscience · 2009Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelf-inactivating retroviral vectors (SIN) are often associated with very low titers. Promoter elements embedded within SIN designs may suppress transcription of packageable retroviral RNA which in turn results in titer reduction. We tested whether this dominant-negative effect involves histone acetylation state. We designed an MLV-derived SIN vector using the cytomegalovirus immediate early enhancer-promoter (CMVIE) as an embedded internal promoter (SINCMV) and transfected the pantropic 293GPG packaging cell line.
resultsThe SINCMV retroviral producer had uniformly very low titers (approximately 10,000 infectious retroparticles per ml). Northern blot showed low levels of expression of retroviral mRNA in producer cells in particular that of packageable RNA transcript. Treatment of the producers with the histone deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A reversed transcriptional suppression and resulted in an average 106.3 +/- 4.6 - fold (P = 0.002) and 15.5 +/- 1.3 - fold increase in titer (P = 0.008), respectively. A histone gel assay confirmed increased histone acetylation in treated producer cells.
conclusionThese results show that SIN retrovectors incorporating strong internal promoters such as CMVIE, are susceptible to transcriptional silencing and that treatment of the producer cells with HDAC inhibitors can overcome this blockade suggesting that histone deacetylation is implicated in the mechanism of transcriptional suppression.
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