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Viruses 2016, 8(12), 333; doi:10.3390/v8120333

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

1
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
2
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA
3
James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
4
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Joanna Parish
Received: 30 September 2016 / Revised: 24 November 2016 / Accepted: 9 December 2016 / Published: 20 December 2016
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [1959 KB, uploaded 20 December 2016]   |  

Abstract

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously (Wechman, S. L. et al. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection. Viruses 2016, 8, 6). In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis. View Full-Text
Keywords: lung cancer; adenovirus; E1b; UV-irradiation; genomics lung cancer; adenovirus; E1b; UV-irradiation; genomics
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MDPI and ACS Style

Wechman, S.L.; Rao, X.-M.; McMasters, K.M.; Zhou, H.S. Adenovirus with DNA Packaging Gene Mutations Increased Virus Release. Viruses 2016, 8, 333.

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