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Comparison of the E3 and L3 regions for arming oncolytic adenoviruses to achieve a high level of tumor-specific transgene expression

Cancer Gene Therapy volume 15, pages 9–17 (2008)Cite this article

Abstract

Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modified splice acceptor sequences that did not necessitate the deletion of any part of the adenoviral genome. Several oncolytic adenoviral vectors were compared in which the transgene was inserted in place of either the E3 or the L3 region. While all vectors had similar viral growth and cytotoxicity characteristics, the highest level of transgene expression was observed from a vector in which the transgene had been inserted downstream of the L3 23K protease gene, the Ad-23K-GM vector. Notably, no transgene expression occurred with this vector in the absence of DNA replication either in vitro or in vivo. In contrast, viruses in which the transgene was inserted into E3 locations exhibited a low level of transgene expression even in the absence of DNA replication. In summary, by utilizing the L3 region for arming oncolytic viruses, higher levels of tumor-specific transgene expression can be obtained without the need to delete any parts of the viral genome.

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Acknowledgements

We thank David L Ennist for helpful discussion with regards to E3 insertion sites, and Peter Working for critical reading of the paper. B Batiste, J Ho, T Langer and S Tanciongco are gratefully acknowledged for their technical assistance.

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Authors and Affiliations

  1. Cell Genesys Inc., South San Francisco, California, CA, USA,

    M Robinson, Y Ge, D Ko, S Yendluri, G Laflamme, L Hawkins & K Jooss

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  1. M Robinson
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Correspondence to M Robinson.

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Robinson, M., Ge, Y., Ko, D. et al. Comparison of the E3 and L3 regions for arming oncolytic adenoviruses to achieve a high level of tumor-specific transgene expression. Cancer Gene Ther 15, 9–17 (2008). https://doi.org/10.1038/sj.cgt.7701093

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