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Extended release of adenovirus from silica implants in vitro and in vivo

Gene Therapy volume 16, pages 103–110 (2009)Cite this article

Abstract

Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 °C and months at +4 °C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.

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Acknowledgements

We thank Eerika Karli, Aila Karioja-Kallio and Johanna Markola for expert assistance. This study was supported by University of Helsinki, Finnish Society of Gastroenterology, EU FP6 THERADPOX and APOTHERAPY, TEKES, HUCH and TUCH Research Funds (EVO), Sigrid Juselius Foundation, Academy of Finland, Emil Aaltonen Foundation, Finnish Cultural Foundation and Finnish Cancer Society. Akseli Hemminki is K Albin Johansson Research Professor of the Foundation for the Finnish Cancer Institute.

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Authors and Affiliations

  1. Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory, University of Helsinki, Helsinki, Finland

    L Kangasniemi, H Moilanen, I Diaconu, A Kanerva, S Pesonen, T Hakkarainen & A Hemminki

  2. HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

    L Kangasniemi, H Moilanen, I Diaconu, A Kanerva, S Pesonen, T Hakkarainen & A Hemminki

  3. DelsiTech Ltd, Turku, Finland

    M Koskinen, M Jokinen & H Jalonen

  4. Turku Center for Biomaterials, University of Turku, Finland

    M Koskinen & M Jokinen

  5. Department of Dermatology, University of Turku, Turku, Finland

    M Toriseva, R Ala-Aho & V-M Kähäri

  6. Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland

    M Toriseva, R Ala-Aho & V-M Kähäri

  7. MediCity Research Laboratory, University of Turku, Turku, Finland

    M Toriseva, R Ala-Aho & V-M Kähäri

  8. AI Virtanen Institute, Kuopio, Finland

    S Ylä-Herttuala

  9. Department of Medicine, University of Kuopio, Kuopio, Finland

    S Ylä-Herttuala

  10. Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

    S Ylä-Herttuala

  11. HUS Pharmacy, Helsinki, Finland

    H Moilanen

  12. Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland

    U-H Stenman

  13. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland

    A Kanerva

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  1. L Kangasniemi
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  2. M Koskinen
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  7. H Jalonen
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Correspondence to A Hemminki.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Kangasniemi, L., Koskinen, M., Jokinen, M. et al. Extended release of adenovirus from silica implants in vitro and in vivo. Gene Ther 16, 103–110 (2009). https://doi.org/10.1038/gt.2008.142

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  • DOI: https://doi.org/10.1038/gt.2008.142

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