The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro

Gene Therapy
M SternE W Alton

Abstract

Trials of gene transfer for cystic fibrosis (CF) are currently underway. However, direct application to the airways may be impeded by the presence of airway secretions. We have therefore assessed the effect of CF sputum on the expression of the reporter gene beta-galactosidase complexed with the cationic liposome DC-Chol/DOPE in a number of cell lines in vitro. Transfection was markedly inhibited in the presence of sputum; the effect was concentration dependent and was only partially ameliorated by removal of sputum with phosphate-buffered saline (PBS) washing before gene transfer. However, treatment of the sputum-covered cells with recombinant human DNase (rhDNase, 50 micrograms/ml) but not with N-acetylcysteine, Nacystelyn, lysine (all 20 mM) or recombinant alginase (0.5 U/ml) significantly (P < 0.005) improved gene transfer. Adenovirus-mediated gene transfer efficiency in the presence of sputum was similarly inhibited, and again, treatment with rhDNase before transfection significantly improved gene transfer (P < 0.005). Transfection of Cos 7 cells in the presence of exogenous genomic DNA alone demonstrated similar inhibition to that observed with sputum and was also ameliorated by pre-treatment of DNA-covered cells with rhD...Continue Reading

Citations

Oct 17, 2001·The Journal of Gene Medicine·J C DaviesE W Alton
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Mary Jayne Kennedy
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Ajay GautamCharles L Densmore
Nov 5, 1999·Biochimica Et Biophysica Acta·S FerrariM Scarpa
Nov 30, 2002·Advanced Drug Delivery Reviews·Stefano FerrariEric W F W Alton
Sep 23, 1998·Molecular Medicine Today·J C DaviesE W Alton
Oct 30, 1998·Molecular Medicine Today·S YeE B Kmiec
Jan 19, 2000·Pharmaceutical Science & Technology Today·I Forbes
Aug 11, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jung Soo SukJustin Hanes
Jun 22, 2005·Journal of Aerosol Medicine : the Official Journal of the International Society for Aerosols in Medicine·A SteimerC-M Lehr
Jan 14, 2003·Annual Review of Physiology·Ryan A Driskell, John F Engelhardt
Nov 9, 2000·American Journal of Respiratory and Critical Care Medicine·N N SandersJ Demeester
Apr 24, 2001·American Journal of Respiratory and Critical Care Medicine·J M ZahmE Puchelle
Feb 19, 2002·American Journal of Respiratory and Critical Care Medicine·Phillip FactorVidas Dumasius
Feb 15, 2005·American Journal of Respiratory and Critical Care Medicine·Isabelle Sermet-GaudelusAleksander Edelman
Aug 2, 2002·American Journal of Respiratory Cell and Molecular Biology·Joseph M Pilewski
Oct 23, 2001·Respiratory Research·M SternE W Alton
Oct 3, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·B Bigger, C Coutelle
Jul 1, 2010·Therapeutic Delivery·Corinna PfeiferCarsten Rudolph
Nov 4, 2000·Expert Opinion on Investigational Drugs·E Alton, C Kitson
May 15, 2012·International Journal of Pharmaceutics·Marcin OdziomekLeon Gradoń
Aug 17, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Basma M IbrahimYoon Yeo
Jun 28, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Abderrahim AissaouiAndrew D Miller
Jan 17, 2009·Advanced Drug Delivery Reviews·Niek SandersJoseph Demeester
May 1, 2007·Clinics in Chest Medicine·Viranuj SueblinvongDaniel J Weiss
Jul 21, 2015·Pulmonary Pharmacology & Therapeutics·Sante Di GioiaMassimo Conese
Aug 17, 1999·Biochemical Pharmacology·L H Naylor
Oct 24, 2006·Pulmonary Pharmacology & Therapeutics·Victoria J Broughton-HeadJanis K Shute
Jan 18, 2003·Paediatric Respiratory Reviews·M Lim, P L Zeitlin
Oct 7, 2004·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Gerd DöringUNKNOWN Consensus Study Group
May 20, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Namho KimJung Soo Suk
Oct 18, 2011·Bioconjugate Chemistry·Olivia M MerkelThomas Kissel
Dec 9, 2016·Human Gene Therapy·Dolan SondhiRonald G Crystal
Aug 6, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel J Weiss
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·P G NooneM R Knowles
Jan 12, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel J WeissJay K Kolls
Jul 4, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel J WeissPhillip Factor

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