Journal article
A NOVEL GENE DELIVERY METHOD TRANSDUCES PORCINE PANCREATIC DUCT EPITHELIAL CELLS
Gene therapy, Vol.21(2), pp.123-130
02/2014
DOI: 10.1038/gt.2013.62
PMCID: PMC3946305
PMID: 24257348
Abstract
Gene therapy offers the possibility to treat pancreatic disease in Cystic Fibrosis (CF), caused by mutations in the cystic fibrosis 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 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 umbilical artery in newborns and via femoral artery at older ages; delivery approaches which can be translated to humans.
Details
- Title: Subtitle
- A NOVEL GENE DELIVERY METHOD TRANSDUCES PORCINE PANCREATIC DUCT EPITHELIAL CELLS
- Creators
- Michelle A Griffin - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242M. Santiago Restrepo - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Marwa Abu-El-Haija - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Tanner Wallen - Department of Otolaryngology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Elizabeth Buchanan - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Tatiana Rokhlina - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Yong Hong Chen - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Paul B McCray - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Beverly L Davidson - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Abhay Divekar - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242Aliye Uc - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA, USA 52242
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.21(2), pp.123-130
- DOI
- 10.1038/gt.2013.62
- PMID
- 24257348
- PMCID
- PMC3946305
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Internal Medicine
- Record Identifier
- 9984047775502771
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