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

V. K. Agrawal, K. M. Copeland, Y. Barbachano, A. Rahim, R. Seth, C. L. White, M. Hingorani, C. M. Nutting, M. Kelly, P. Harris, H. Pandha, A. A. Melcher, R. G. Vile, C. Porter, K. J. Harrington

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)78-92
Number of pages15
JournalGene Therapy
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Agrawal, V. K., Copeland, K. M., Barbachano, Y., Rahim, A., Seth, R., White, C. L., Hingorani, M., Nutting, C. M., Kelly, M., Harris, P., Pandha, H., Melcher, A. A., Vile, R. G., Porter, C., & Harrington, K. J. (2009). Microvascular free tissue transfer for gene delivery: In vivo evaluation of different routes of plasmid and adenoviral delivery. Gene Therapy, 16(1), 78-92. https://doi.org/10.1038/gt.2008.140