ORIGINAL ARTICLE
442
Journal of
l
Cellular
Physiology
CFTR Gene Transfer to Human
Cystic Fibrosis Pancreatic Duct
Cells Using a Sendai Virus Vector
ZOLTÁN RAKONCZAY JR,1,2 PÉTER HEGYI,1,2 MAMORU HASEGAWA,3 MAKOTO INOUE,3
JUN YOU,3 AKIHIRO IIDA,3 IMRE IGNÁTH,2 ERIC W.F.W. ALTON,4 UTA GRIESENBACH,4
GABRIELLA ÓVÁRI,5 JÁNOS VÁG,5 ANA C. DA PAULA,6 RUSSELL M. CRAWFORD,8
GÁBOR VARGA,5 MARGARIDA D. AMARAL,6,7 ANIL MEHTA,8 JÁNOS LONOVICS,2
BARRY E. ARGENT,1 AND MICHAEL A. GRAY1*
1Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, United Kingdom
2First Department of Medicine, University of Szeged, Szeged, Hungary
3DNAVEC Corporation, Tsukuba, Ibaraki, Japan
4Department of Gene Therapy, National Heart and Lung Institute, Imperial College, London, United Kingdom
5Molecular Oral Biology Research Group, Department of Oral Biology,
Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary
6Centre of Human Genetics, National Institute of Health, Lisboa, Portugal
7Department of Chemistry & Biochemistry, University of Lisboa, Lisboa, Portugal
8Division of Maternal and Child Health Sciences, Ninewells Hospital Medical School, Dundee, Scotland, United Kingdom
Cystic fibrosis (CF) is a fatal inherited disease caused by the absence or dysfunction of the CF transmembrane conductance regulator
(CFTR) Cl channel. About 70% of CF patients are exocrine pancreatic insufficient due to failure of the pancreatic ducts to secrete a
HCO3 -rich fluid. Our aim in this study was to investigate the potential of a recombinant Sendai virus (SeV) vector to introduce normal
CFTR into human CF pancreatic duct (CFPAC-1) cells, and to assess the effect of CFTR gene transfer on the key transporters involved in
HCO3 transport. Using polarized cultures of homozygous F508del CFPAC-1 cells as a model for the human CF pancreatic ductal
epithelium we showed that SeV was an efficient gene transfer agent when applied to the apical membrane. The presence of functional
CFTR was confirmed usi