Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog

Chang S. Lim, Gregory D. Chapman, Roger S. Gammon, Joseph B. Muhlestein, Robert P. Bauman, Richard S. Stack, Judith L. Swain

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding β-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of β-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous β-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)2007-2011
Number of pages5
JournalCirculation
Volume83
Issue number6
DOIs
StatePublished - Jun 1991

Keywords

  • Genetics
  • Lipofection
  • Luciferase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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