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- Title
Adenovirus with DNA Packaging Gene Mutations Increased Virus Release.
- Authors
Wechman, Stephen L.; Xiao-Mei Rao; McMasters, Kelly M.; Heshan Sam Zhou
- 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.
- Subjects
ADENOVIRUSES; CANCER cell growth; CANCER cell motility; ONCOLOGIC surgery; HUMAN adenoviruses
- Publication
Viruses (1999-4915), 2016, Vol 8, Issue 12, p333
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v8120333