A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis

The New England Journal of Medicine
M R KnowlesK R Jones

Abstract

Cystic fibrosis is a monogenic disease that deranges multiple systems of ion transport in the airways, culminating in chronic infection and destruction of the lung. The introduction of a normal copy of the cystic fibrosis transmembrane conductance regulator (CFTR) gene into the airway epithelium through gene transfer is an attractive approach to correcting the underlying defects in patients with cystic fibrosis. We tested the feasibility of gene therapy using adenoviral vectors in the nasal epithelium of such patients. An adenoviral vector containing the normal CFTR complementary DNA in four logarithmically increasing doses (estimated multiplicity of infection, 1, 10, 100, and 1000), or vehicle alone, was administered in a randomized, blinded fashion to the nasal epithelium of 12 patients with cystic fibrosis. Gene transfer was quantitated by molecular techniques that detected the expression of CFTR messenger RNA and by functional measurements of transepithelial potential differences (PDs) to assess abnormalities of ion transport specific to cystic fibrosis. The safety of this treatment was monitored by nasal lavage and biopsy to assess inflammation and vector replication. The adenoviral vector was detected in nasal-lavage flui...Continue Reading

References

Feb 1, 1976·The Journal of Urology·M A Mufson, R B Belshe
Jan 1, 1977·Archives of Environmental Contamination and Toxicology·H N NiggA H Blagg
Dec 1, 1992·The Journal of Clinical Investigation·J F EngelhardtJ M Wilson
Oct 1, 1992·Statistics in Medicine·S L Zeger, K Y Liang
Jul 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P M Quinton
Jan 1, 1988·The Journal of Infectious Diseases·R M NaclerioJ M Gwaltney
May 1, 1988·The American Review of Respiratory Disease·F W HendersonD Graham
Sep 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·J H WiddicombeW E Finkbeiner
Oct 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·M J StuttsR C Boucher
Dec 17, 1981·The New England Journal of Medicine·M KnowlesR Boucher
Jan 1, 1995·American Journal of Respiratory and Critical Care Medicine·E D BatemanJ C Hogg
Mar 1, 1995·The Journal of Infectious Diseases·T L NoahS Becker
Jun 1, 1994·American Journal of Respiratory Cell and Molecular Biology·R R MercerJ D Crapo
Aug 1, 1994·American Journal of Respiratory and Critical Care Medicine·R C Boucher
Jul 1, 1993·American Journal of Respiratory Cell and Molecular Biology·J L CurtisH B Kaltreider
Aug 1, 1993·The American Review of Respiratory Disease·D B PedenM A Kaliner

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Citations

Jul 29, 1996·International Journal of Cancer. Journal International Du Cancer·M V Blagosklonny, W S el-Deiry
Nov 5, 1997·International Journal of Cancer. Journal International Du Cancer·D S ReedC V Jongeneel
Mar 1, 1996·Pediatric Pulmonology·R C Stern
Apr 25, 2001·The Journal of Gene Medicine·E S ScottW H Colledge
Mar 12, 2002·Pediatric Pulmonology·D Geddes
Sep 1, 1996·Cancer Metastasis Reviews·R G Vile
Jul 1, 1997·Journal of Assisted Reproduction and Genetics·V H Eisenberg, J G Schenker
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Mary Jayne Kennedy
Dec 16, 2004·European Journal of Nuclear Medicine and Molecular Imaging·Gang NiuFrederick E Domann
Jan 11, 2012·Protein & Cell·Huibi CaoJim Hu
Mar 1, 1996·Trends in Genetics : TIG·R C Boucher
Nov 4, 2004·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Adam M ZanationWendell G Yarbrough
Sep 13, 2003·Fertility and Sterility·Gaurang S Daftary, Hugh S Taylor
Feb 20, 1998·Physiology & Behavior·D Holditch-DavisR W Helms
Feb 28, 2003·Lancet·Felix Ratjen, Gerd Döring
Jun 15, 1999·Trends in Pharmacological Sciences·D L Ennist
Apr 25, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Radi Hejazi, Mansoor Amiji
Sep 19, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·K W LeongJ T August
Nov 24, 2001·Advanced Drug Delivery Reviews·G Borchard
Nov 30, 2002·Advanced Drug Delivery Reviews·Stefano FerrariEric W F W Alton
Jun 6, 2000·Advanced Drug Delivery Reviews·E Alton, D Geddes
Jun 6, 2000·Advanced Drug Delivery Reviews·X XingM Hung
Jun 6, 2000·Advanced Drug Delivery Reviews·K M Bowie, P L Chang
Jun 6, 2000·Advanced Drug Delivery Reviews·R J LevyJ Bonadio
Oct 11, 2003·Biotechnology Advances·Sally McTaggart, Mohamed Al-Rubeai
Sep 23, 1998·Molecular Medicine Today·J C DaviesE W Alton
Apr 14, 1999·Molecular Medicine Today·K Walsh, M Sata
Jun 23, 1999·Molecular Medicine Today·C Sansom
Nov 1, 1995·Nature Medicine·R S Williams
Sep 28, 1995·The New England Journal of Medicine·J M Leiden
Feb 1, 1996·The New England Journal of Medicine·E Alton, D M Geddes
Jul 18, 1996·The New England Journal of Medicine·B W Ramsey
Feb 13, 1997·The New England Journal of Medicine·R C Stern
Feb 6, 2004·The New England Journal of Medicine·Steven D FreedmanBrian P O'Sullivan
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·L NaldiniI M Verma

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