کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1939708 | 1050765 | 2006 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Murine leukemia virus vector integration favors promoter regions and regional hot spots in a human T-cell line Murine leukemia virus vector integration favors promoter regions and regional hot spots in a human T-cell line](/preview/png/1939708.png)
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 (±5 kb), near CpG islands (±1 kb), and within the first intron of RefSeq genes. We also identified MLV integration hot spots that contained three or more integrations within a 100 kb 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.
Journal: Biochemical and Biophysical Research Communications - Volume 345, Issue 3, 7 July 2006, Pages 1099–1107