Vector-specific complementation profiles of two independent primary defects in cystic fibrosis airways

Human Gene Therapy
Y ZhangJ F Engelhardt

Abstract

Cystic fibrosis (CF) lung disease has been linked to multiple primary defects in airway epithelia caused by a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) gene. These defects include altered Cl- and Na+ permeability as well as intracellular defects in glycoprotein processing. This apparent diversity in CFTR function is reflected in the complex patterning of CFTR expression in airway epithelia. Such complexities present challenges in the design of CF gene therapies that are capable of reconstituting the endogenous patterns of CFTR gene expression in appropriate target cells. Using a human bronchial xenograft model of the CF airway, we have evaluated the efficacy of recombinant adenoviral and cationic liposome-mediated gene transfer to correct Cl- permeability and mucous sulfation defects found in CF lung disease. Results from these studies demonstrated a clear vector-specific complementation profile for these two defects that was dependent on the type of cell transduced and the level of transgene expression. Single-dose administration of recombinant adenovirus effectively transduced high levels of CFTR transgene expression in 11 +/- 1% of epithelial cells and was capable of correcting cAMP-induced cha...Continue Reading

References

Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·B C TrapnellR G Crystal
Jan 1, 1991·Physiological Reviews·E H Larsen
Jan 1, 1990·Pediatric Pulmonology·M S Zach
Jul 1, 1986·The Journal of Physiology·J E Langridge-Smith
Nov 1, 1981·Analytical Biochemistry·P W ChengM Bruce
Aug 11, 1995·Science·M J StuttsR C Boucher
Jan 1, 1994·Human Molecular Genetics·W K O'Neal, A L Beaudet
Nov 1, 1995·Pflügers Archiv : European journal of physiology·K KunzelmannR Greger
May 1, 1996·The American Journal of Physiology·Y ZhangJ F Engelhardt

❮ Previous
Next ❯

Citations

Nov 30, 2002·Advanced Drug Delivery Reviews·Stefano FerrariEric W F W Alton
Oct 7, 2004·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Anne VankeerberghenJean-Jacques Cassiman
Dec 28, 1999·Human Gene Therapy·K SchughartH V Kolbe
Jan 14, 2003·Annual Review of Physiology·Ryan A Driskell, John F Engelhardt
Feb 15, 2005·American Journal of Respiratory and Critical Care Medicine·Isabelle Sermet-GaudelusAleksander Edelman
Feb 13, 2001·American Journal of Respiratory Cell and Molecular Biology·X WangJ F Engelhardt
Jan 29, 2005·American Journal of Respiratory Cell and Molecular Biology·Shih-Hsing LeirAnn Harris
May 20, 1999·The Journal of Clinical Investigation·N KälinB Tümmler
Jun 5, 2003·Expert Opinion on Biological Therapy·Assem G ZiadyMichael W Konstan
Feb 13, 2015·Human Gene Therapy. Clinical Development·Ziying YanJohn F Engelhardt
Feb 3, 2015·The Journal of Clinical Investigation·Jinghua LiuLane L Clarke
Oct 17, 2001·The Journal of Gene Medicine·J C DaviesE W Alton
Apr 23, 2008·Current Protocols in Human Genetics·D DuanJ F Engelhardt
Jul 16, 2013·Current Protocols in Human Genetics·Nicholas W Keiser, John F Engelhardt
Sep 26, 2000·American Journal of Physiology. Cell Physiology·G A GibsonO A Weisz
Feb 10, 1999·The American Journal of Physiology·Y Zhang, J F Engelhardt

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.