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Microvascular free tissue transfer for gene delivery: in vivo evaluation of different routes of plasmid and adenoviral delivery

Gene Therapy volume 16, pages 78–92 (2009)Cite this article

Abstract

Transfer of healthy autologous tissue as a microvascular free flap facilitates reconstruction during ablative cancer surgery. In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topography and duration of luciferase gene expression after plasmid and adenoviral delivery in rat superficial inferior epigastric (SIE) flaps. For plasmid delivery, luciferase expression was significantly increased by all transduction routes (topical, intraflap injection, intravascular) (P<0.01) at day 1, but not at day 7. The spread of luciferase expression was significantly different between the 4 groups at 1 day (P=0.026) and was greatest for flaps transduced by intravascular injection. For adenoviral transduction, total radiance was significantly different between the transduced groups at 1, 14 and 28 days (P<0.05 for all comparisons). The highest levels of radiance were seen in the intravascular group. There was a statistically significant difference in the spread of light emission between the 3 groups at 1 (P=0.009) and 14 (P=0.013) days, but this was no longer evident at 28 days. Intravascular adenoviral delivery yields high-level, diffuse and durable gene expression in rat SIE flaps and is suitable for examination in therapeutic models.

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Authors and Affiliations

  1. Chester Beatty Laboratories, The Institute of Cancer Research, London, UK

    V K Agrawal, K M Copeland, A Rahim, R Seth, C L White, M Hingorani, C Porter & K J Harrington

  2. Head and Neck Unit, Royal Marsden Hospital, London, UK

    V K Agrawal, C M Nutting, M Kelly, P Harris & K J Harrington

  3. Department of Statistics, Royal Marsden Hospital, Sutton, UK

    Y Barbachano

  4. University of Surrey, Guildford, UK

    H Pandha

  5. St James's University Hospital, Leeds, UK

    A A Melcher

  6. St George's Hospital, Cranmer Terrace, London, UK

    R G Vile

Authors
  1. V K Agrawal
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  2. K M Copeland
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  3. Y Barbachano
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  4. A Rahim
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  5. R Seth
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  6. C L White
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  7. M Hingorani
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  8. C M Nutting
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  9. M Kelly
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  10. P Harris
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  11. H Pandha
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  12. A A Melcher
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  13. R G Vile
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  14. C Porter
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  15. K J Harrington
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Corresponding author

Correspondence to K J Harrington.

Additional information

The authors wish to recognise the key contribution made by the late Mr Martin Kelly to these studies. Martin was instrumental in developing our concepts of using flaps for therapeutic purposes in patients with head and neck cancer and we will deeply miss his insight in further developments in this area.

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Agrawal, V., Copeland, K., Barbachano, Y. et al. Microvascular free tissue transfer for gene delivery: in vivo evaluation of different routes of plasmid and adenoviral delivery. Gene Ther 16, 78–92 (2009). https://doi.org/10.1038/gt.2008.140

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  • DOI: https://doi.org/10.1038/gt.2008.140

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