ArticleMolecular therapy. Nucleic acids2012
Epigenetic modification of the repair donor regulates targeted gene correction.
Article in Molecular therapy. Nucleic acids, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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.
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Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- Transcription-coupled donor DNA expression increases homologous recombination for efficient genome editing.Nucleic acids research · 2022Article
- Novel fluorescent genome editing reporters for monitoring DNA repair pathway utilization at endonuclease-induced breaks.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Optimizing design of vectors is critical to effective gene therapy. In targeted gene correction (TGC), cleavage of chromosomal DNA near a mutation stimulates homology-directed repair of a target gene using a donor provided in trans. We have systematically addressed epigenetic parameters of donor design, using a flow-based assay to quantify correction frequencies and expression levels of a green fluorescent protein (GFP) reporter gene in a human cell line. We show that active transcription of the donor increased correction frequency by threefold, establishing that a proximal promoter enhances donor use. Conversely, CpG methylation of the donor diminished correction frequency and reduced expression of the repaired gene. However, bisulfite sequencing of the target revealed no transfer of methylation marks during repair with a methylated donor. Treatment with histone deacetylase (HDAC) inhibitors can partially compensate for epigenetic inactivation, suggesting a role for class I and II HDACs in regulation of donor use. These results establish that epigenetic status of a trans-donor determines both the efficiency and outcome of gene correction, and identify and clarify parameters that should guide donor design for targeted gene therapy.Molecular Therapy - Nucleic Acids (2012) 1, e49; doi:10.1038/mtna.2012.42; published online 23 October 2012.
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Registered trials
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