A novel gene delivery method transduces porcine pancreatic duct epithelial cells

Gene Ther. 2014 Feb;21(2):123-30. doi: 10.1038/gt.2013.62. Epub 2013 Nov 21.


Gene therapy offers the possibility to treat pancreatic disease in cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene; however, gene transfer to the pancreas is untested in humans. The pancreatic disease phenotype is very similar between humans and pigs with CF; thus, CF pigs create an excellent opportunity to study gene transfer to the pancreas. There are no studies showing efficient transduction of pig pancreas with gene-transfer vectors. Our objective is to develop a safe and efficient method to transduce wild-type (WT) porcine pancreatic ducts that express CFTR. We catheterized the umbilical artery of WT newborn pigs and delivered an adeno-associated virus serotype 9 vector expressing green-fluorescent protein (AAV9CMV.sceGFP) or vehicle to the celiac artery, the vessel that supplies major branches to the pancreas. This technique resulted in stable and dose-dependent transduction of pancreatic duct epithelial cells that expressed CFTR. Intravenous (IV) injection of AAV9CMV.sceGFP did not transduce the pancreas. Our technique offers an opportunity to deliver the CFTR gene to the pancreas of CF pigs. The celiac artery can be accessed via the umbilical artery in newborns and via the femoral artery at older ages--delivery approaches that can be translated to humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Celiac Artery / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Dependovirus / genetics
  • Epithelial Cells / metabolism*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects*
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Injections, Intravenous
  • Pancreatic Ducts / metabolism*
  • Swine
  • Transduction, Genetic / methods*


  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Green Fluorescent Proteins