| Literature DB >> 16713998 |
Tomonori Tsukahara1, Hideyuki Agawa, Sayori Matsumoto, Mizuho Matsuda, Shuichi Ueno, Yuki Yamashita, Koichiro Yamada, Nobuyuki Tanaka, Katsuhiko Kojima, Toshikazu Takeshita.
Abstract
Genomic analysis of integration will be important in evaluating the safety of human gene therapy with retroviral vectors. Here, we investigated MLV vector integration sites in human T-cells, since they are amenable to gene transfer studies, and have been used therapeutically in clinical trials. We mapped 340 MLV vector integration sites in the infected human T-cell clones we established. The data showed that MLV preferred integration near the transcription start sites (+/-5kb), near CpG islands (+/-1kb), and within the first intron of RefSeq genes. We also identified MLV integration hot spots that contained three or more integrations within a 100kb region. RT-PCR revealed that mRNA-levels of T-cell clones that contained MLV integrations near transcription start sites or introns were dysregulated compared to the uninfected cells. These studies help define the profile of MLV integration in T-cells and the risks associated with MLV-based gene therapy.Entities:
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Year: 2006 PMID： 16713998 DOI： 10.1016/j.bbrc.2006.05.007
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575