Adenovirus-mediated gene transfer to the transplanted piglet heart after intracoronary injection

Frank Griscelli, Emre Belli, Paule Opolon, Karine Musset, Elisabeth Connault, Michel Perricaudet, Alain Serraf, Guy Michel Mazmanian, Thierry Ragot

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The advent of cardiac gene therapy in clinical practice requires a more efficient and safer myocardial gene delivery in large animals. A new approach to adenovirus-mediated intracoronary gene transfer in the piglet, using a heterotopic heart transplantation model, was designed to maximize the duration of contact between the vector and the heart in noncoronary flow conditions. Methods: Recombinant adenoviruses harboring a nucleus-localized β-galactosidase gene under the control of a viral promoter were injected into the coronary vessels of the harvested hearts at a dose ranging from 1010 to 2 × 1011 pfu. The graft was maintained for 75 min in saline solution and then implanted in the abdomen of recipients. Gene transfer to allografts was evaluated 4 days after grafting by immunohistochemical and enzymatic analysis of β-galactosidase expression. Results: Transgene expression was detected in all cardiac areas and up to 64, 44, 32, and 15% of positive nuclei were estimated in the left ventricle wall in four animals out of eleven. In the remaining animals, transgene expression was focally distributed, mainly in the left ventricle wall. PCR analysis revealed the presence of adenoviral sequences, albeit minimal, in exposed organs such as the liver and lung. Conclusions: This procedure demonstrated that direct intracoronary gene transfer can be achieved using an ex vivo gene transfer strategy.

Original languageEnglish
Pages (from-to)109-119
Number of pages11
JournalJournal of Gene Medicine
Volume5
Issue number2
DOIs
StatePublished - Feb 2003
Externally publishedYes

Keywords

  • Adenovirus
  • Gene transfer
  • Heart transplantation
  • Intracoronary injection
  • Pig

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