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Semliki Forest virus biodistribution in tumor-free and 4T1 mammary tumor-bearing mice: a comparison of transgene delivery by recombinant virus particles and naked RNA replicon

Cancer Gene Therapy volume 19, pages 579–587 (2012)Cite this article

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Abstract

Semliki Forest virus (SFV) vectors are promising tools for cancer gene therapy because they ensure a high level of transgene expression and a rapid and strong cytopathic effect. However, broad tissue tropism and transient expression make it more difficult to develop an optimal cancer treatment strategy. In this study, we have compared the distribution of recombinant SFV particles (recSFV) and naked viral RNA replicon (recRNA) in tumor-free and 4T1 mammary tumor-bearing mice as a consequence of different vector administration strategies. The high potential of SFV recRNA as a biosafe approach for the development of therapeutic treatment was demonstrated. Intravenous (i.v.) inoculation of recRNA provided primary brain targeting in both tumor-free and 4T1 tumor mouse models, but local intratumoral inoculation revealed a high expression level in tumors. Moreover, we observed the predominant tumor targeting of recSFV at a reduced viral dose on i.v. and intraperitoneal (i.p.) virus inoculation, whereas the dose increase led to a broad virus distribution in mice. To prolong transgene expression, we have tested several i.v. and i.p. reinoculation strategies. A detailed evaluation of vector distribution and readministration properties could have an impact on cancer gene therapy clinical trial safety and efficacy.

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Acknowledgements

We thank Professor A Merits and his group for sharing the pSFV/Enh.Luc DNA plasmid, and for critically reading the manuscript and useful suggestions. We also acknowledge Professor P Pumpens and his lab members for helpful discussions and excellent technical assistance. We are grateful to Dr I Shestakova and her group for useful advice in 4T1 model development. The publishing expenses were covered by ERDF project Nr. 2010/0196/2DP/2.1.1.2.0/10/APIA/VIAA/004. This study was supported by The Latvian National Research Programme 2010–2013, “BIOMEDICINE”.

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Authors and Affiliations

  1. Department of Protein Engineering, Biomedical Research and Study Centre, Riga, Latvia

    J Vasilevska, D Skrastina, K Spunde, T Kozlovska & A Zajakina

  2. Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

    H Garoff

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  1. J Vasilevska
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Correspondence to A Zajakina.

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Vasilevska, J., Skrastina, D., Spunde, K. et al. Semliki Forest virus biodistribution in tumor-free and 4T1 mammary tumor-bearing mice: a comparison of transgene delivery by recombinant virus particles and naked RNA replicon. Cancer Gene Ther 19, 579–587 (2012). https://doi.org/10.1038/cgt.2012.37

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