Preprint Article Version 1 This version not peer reviewed

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

Version 1 : Received: 18 December 2016 / Approved: 19 December 2016 / Online: 19 December 2016 (09:33:20 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Viruses 2016, 8, 333
DOI: 10.3390/v8120333

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 [1]. 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.

Subject Areas

lung cancer; adenovirus; E1b; UV-irradiation; genomics

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