A second dose of a CFTR cDNA-liposome complex is as effective as the first dose in restoring cAMP-dependent chloride secretion to null CF mice trachea

Gene Therapy
C A GoddardW H Colledge

Abstract

Phase I clinical trials have provided encouraging data suggesting that gene transfer could provide a treatment for cystic fibrosis (CF). However, for all the current viral and nonviral vectors used to deliver the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the duration of CFTR expression is limited, necessitating a repeat dosing regimen to provide a long-term treatment. This study was performed to determine whether a second delivery of a CFTR cDNA-liposome complex could result in a similar level of functional CFTR expression observed after a single delivery and to assess whether the deliveries produced adverse inflammatory responses. CFTR functional expression was assessed by short circuit current measurements of tracheas taken from CF null mice (Cftrtm1Cam) treated with a CFTR cDNA-liposome complex in the upper airways. Mice receiving two deliveries of this complex, the second after the response to the first had declined, showed cAMP-stimulated chloride currents which were not significantly different from normal tracheas or tissues assayed after a single dose of the complex. This double treatment was well tolerated with no discernible inflammation of lung tissue.

Citations

Aug 12, 1999·European Journal of Pharmacology·U Rudolph, H Möhler
Nov 5, 2002·Trends in Pharmacological Sciences·Alan W Cuthbert
Nov 30, 2002·Advanced Drug Delivery Reviews·Stefano FerrariEric W F W Alton
May 10, 2001·Drug Discovery Today·T J. AnchordoquyT K. Carson
Apr 29, 1998·The Journal of Clinical Investigation·L W LaiY H Lien
Jan 13, 1999·Clinical Otolaryngology and Allied Sciences·S M Graham
Nov 4, 2000·Expert Opinion on Investigational Drugs·E Alton, C Kitson
Mar 26, 2003·Clinical and Experimental Immunology·S FerrariE Alton
Dec 9, 2016·Human Gene Therapy·Dolan SondhiRonald G Crystal
Jan 19, 2000·The Journal of Laboratory and Clinical Medicine·A J MoserJ J Roslyn
Jul 29, 2008·Journal of Cellular and Molecular Medicine·George KotzamanisClare Huxley
Apr 6, 2007·The Journal of Gene Medicine·Ian A PringleStephen C Hyde
Oct 29, 2005·American Journal of Respiratory and Critical Care Medicine·Judy M Hickman-DavisSadis Matalon
Jun 28, 2008·Health Care Management Science·Paul AvillachMarius Fieschi
Jan 1, 2010·Acta Biochimica Et Biophysica Sinica·Stefania XenariouEric W F W Alton
Apr 23, 2008·Current Protocols in Human Genetics·M WhitemoreL Huang
Mar 9, 2000·Journal of Pharmaceutical Sciences·T J Anchordoquy, G S Koe
Nov 12, 2009·Pharmacology & Therapeutics·James L Kreindler

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