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Mol. Cells 2012; 33(5): 525-531

Published online May 31, 2012

https://doi.org/10.1007/s10059-012-0038-x

© The Korean Society for Molecular and Cellular Biology

Retroviral Infection of hES Cells Produces Random-like Integration Patterns

Kwang-il Lim1,2,*

1Departments of Chemical Engineering and Bioengineering and The Helen Wills Neuroscience Institute, University of California, Berkeley, USA, 2Department of Medical and Pharmaceutical Sciences, College of Science, Sookmyung Women’s University, Seoul 140-742, Korea

Correspondence to : *Correspondence: klim@sm.ac.kr

Received: February 6, 2012; Revised: March 11, 2012; Accepted: March 14, 2012

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.

Keywords gene therapy, human embryonic stem cells, oncogenic potential, overall chromatin structure, retroviral integration patterns

Article

Research Article

Mol. Cells 2012; 33(5): 525-531

Published online May 31, 2012 https://doi.org/10.1007/s10059-012-0038-x

Copyright © The Korean Society for Molecular and Cellular Biology.

Retroviral Infection of hES Cells Produces Random-like Integration Patterns

Kwang-il Lim1,2,*

1Departments of Chemical Engineering and Bioengineering and The Helen Wills Neuroscience Institute, University of California, Berkeley, USA, 2Department of Medical and Pharmaceutical Sciences, College of Science, Sookmyung Women’s University, Seoul 140-742, Korea

Correspondence to:*Correspondence: klim@sm.ac.kr

Received: February 6, 2012; Revised: March 11, 2012; Accepted: March 14, 2012

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.

Keywords: gene therapy, human embryonic stem cells, oncogenic potential, overall chromatin structure, retroviral integration patterns

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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