Please use this identifier to cite or link to this item:
https://doi.org/10.1038/gt.2014.11
DC Field | Value | |
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dc.title | Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity | |
dc.contributor.author | Sivalingam, J. | |
dc.contributor.author | Phan, T.T. | |
dc.contributor.author | Kon, O.L. | |
dc.date.accessioned | 2014-11-26T08:29:01Z | |
dc.date.available | 2014-11-26T08:29:01Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Sivalingam, J., Phan, T.T., Kon, O.L. (2014). Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity. Gene Therapy 21 (4) : 402-412. ScholarBank@NUS Repository. https://doi.org/10.1038/gt.2014.11 | |
dc.identifier.issn | 14765462 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/110142 | |
dc.description.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. © 2014 Macmillan Publishers Limited. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/gt.2014.11 | |
dc.source | Scopus | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE | |
dc.description.doi | 10.1038/gt.2014.11 | |
dc.description.sourcetitle | Gene Therapy | |
dc.description.volume | 21 | |
dc.description.issue | 4 | |
dc.description.page | 402-412 | |
dc.description.coden | GETHE | |
dc.identifier.isiut | 000333777900008 | |
Appears in Collections: | Staff Publications |
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