Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential
In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1-...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 July 2012
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| In: |
Journal of virology
Year: 2012, Volume: 86, Issue: 19, Pages: 10418-10431 |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/JVI.00848-12 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1128/JVI.00848-12 Verlag, Volltext: https://jvi.asm.org/content/86/19/10418 
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| Author Notes: | Nazim El-Andaloussi, Serena Bonifati, Johanna K. Kaufmann, Laurent Mailly, Laurent Daeffler, François Deryckère, Dirk M. Nettelbeck, Jean Rommelaere, and Antonio Marchini |
| Summary: | In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells. |
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| Item Description: | Published ahead of print 11 July 2012 Gesehen am 27.06.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/JVI.00848-12 |