Please use this identifier to cite or link to this item:
Title: Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity
Authors: Sivalingam, J.
Phan, T.T.
Kon, O.L. 
Issue Date: 2014
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.
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.
Source Title: Gene Therapy
ISSN: 14765462
DOI: 10.1038/gt.2014.11
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Nov 23, 2022


checked on Nov 23, 2022

Page view(s)

checked on Nov 24, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.