ArticleGene therapy2014
Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity.
Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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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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
4 citing papers in PubMed, 5 citations in OpenAlex.
- Global mapping of binding sites for phic31 integrase in transgenic maden-darby bovine kidney cells using ChIP-seq.Hereditas · 2019Article
- Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment.Journal of cellular and molecular medicine · 2018Article
- Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Techniques enabling precise genome modifications enhance the safety of gene-based therapy. DLC1 is a hot spot for phiC31 integrase-mediated transgene integration in vitro and in vivo. Here we show that integration of a coagulation factor VIII transgene into intron 7 of DLC1 supports durable expression of factor VIII in primary human umbilical cord-lining epithelial cells. Oligoclonal cells with factor VIII transgene integrated in DLC1 did not have altered expression of DLC1 or neighbouring genes within a 1-Mb interval. Only 1.9% of all expressed genes were transcriptionally altered; most were downregulated and mapped to cell cycle and DNA repair pathways. DLC1-integrated cells were not tumourigenic in vivo and were normal by high-resolution genomic DNA copy number analysis. Our data identify DLC1 as a locus for durable transgene expression that does not incur features of insertional oncogenesis, thus expanding options for developing ex vivo cell therapy mediated by site-specific integration methods.
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Registered trials
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