Retroviral infection of hES cells produces random-like integration patterns
- Authors
- Lim, Kwang-il
- Issue Date
- May-2012
- Publisher
- KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- Keywords
- gene therapy; human embryonic stem cells; oncogenic potential; overall chromatin structure; retroviral integration patterns
- Citation
- MOLECULES AND CELLS, v.33, no.5, pp 525 - 531
- Pages
- 7
- Journal Title
- MOLECULES AND CELLS
- Volume
- 33
- Number
- 5
- Start Page
- 525
- End Page
- 531
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/11921
- DOI
- 10.1007/s10059-012-0038-x
- ISSN
- 1016-8478
0219-1032
- Abstract
- Retroviral integration provides us with a powerful tool to realize prolonged gene expressions that are often critical to gene therapy. However, the perturbation of gene regulations in host cells by viral genome integration can lead to detrimental effects, yielding cancer. The oncogenic potential of retroviruses is linked to the preference of retroviruses to integrate into genomic regions that are enriched in gene regulatory elements. To better navigate the double-edged sword of retroviral integration we need to understand how retroviruses select their favored genomic loci during infections. In this study I showed that in addition to host proteins that tether retroviral pre-integration complexes to specific genomic regions, the epigenetic architecture of host genome might strongly affect retroviral integration patterns. Specifically, retroviruses showed their characteristic integration preference in differentiated somatic cells. In contrast, retroviral infections of hES cells, which are known to display decondensed chromatin, produced random-like integration patterns lacking of strong preference for regulatory-element-rich genomic regions. Better identification of the cellular and viral factors that determine retroviral integration patterns will facilitate the design of retroviral vectors for safer use in gene therapy.
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