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Genes 2017, 8(9), 232; doi:10.3390/genes8090232

Effects of Cellular Methylation on Transgene Expression and Site-Specific Integration of Adeno-Associated Virus

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Received: 22 August 2017 / Revised: 7 September 2017 / Accepted: 8 September 2017 / Published: 18 September 2017
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

DNA methylation is a major epigenetic event that affects not only cellular gene expression but that also has the potential to influence bacterial and viral DNA in their host-dependent functions. Adeno-associated virus (AAV) genome contains a high degree of CpG sequences capable of methylation in its terminal repeat sequences, which are the sole elements retained in AAV-based vectors used in gene therapy. The present study determined the influence of methylation status of the host cell on wild type (wt) AAV integration and recombinant (r) AAV transgene expression in HeLa cells. Results of the study indicated that hypo-methylation significantly enhanced both wtAAV chromosomal integration and transgene expression of rAAV. A direct influence of methylation on AAV integration was further confirmed by methylating the AAVS1 integration sites prior to viral infection with DNA trans-complementation assay. These results signify the importance of epigenetic status of target cells as one of the key factors in long-term transgene expression in AAV gene therapy. View Full-Text
Keywords: adeno-associated virus; 5-Azacytidine; gene expression; site-specific integration adeno-associated virus; 5-Azacytidine; gene expression; site-specific integration
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MDPI and ACS Style

Chanda, D.; Hensel, J.A.; Higgs, J.T.; Grover, R.; Kaza, N.; Ponnazhagan, S. Effects of Cellular Methylation on Transgene Expression and Site-Specific Integration of Adeno-Associated Virus. Genes 2017, 8, 232.

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