The UK Cystic Fibrosis Gene Therapy Consortium
Who are we
Profiles of the Consortium Strategy Group
Frequently Asked Questions
All Trials Registered Initiative
About this Website
The Cystic Fibrosis Trust
Just Gene Therapy
What is Cystic Fibrosis?
History of Cystic Fibrosis
Discovery of the CFTR Gene
What causes Cystic Fibrosis?
CFTR Protein Structure
Introduction to Gene Therapy
Why use Gene Therapy to Treat CF?
Other CF Gene Therapy Groups
Successful Applications of Gene Therapy
CF Gene Therapy Clinical Trials
GL67A pGM169 - Our first clinical trial product
The Tracking Study
The Run In Study
Single Dose Clinical Trial (2009-2011)
Multi Dose Clinical Trial (2012-2014)
Multi Dose Clinical Trial Protocol
Public Meeting, 30 May 2015
Nonviral Vector Development
Aerosol Delivery of Gene Transfer Vectors
Lentiviral Vector Development
Optimizing aerosol gene delivery and expression in the ovine lung.
McLachlan G et al., Mol Ther. 2007 Feb;15(2):348-54.
Bacterial DNA is implicated in the inflammatory response to delivery of DNA/DOTAP to mouse lungs.
McLachlan G et al., Gene Ther. 2000 Mar;7(5):384-92.
Laboratory and clinical studies in support of cystic fibrosis gene therapy using pCMV-CFTR-DOTAP.
McLachlan G et al., Gene Ther. 1996 Dec;3(12):1113-23.
Evaluation in vitro and in vivo of cationic liposome-expression construct complexes for cystic fibrosis gene therapy.
McLachlan G et al., Gene Ther. 1995 Nov;2(9):614-22.
Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung.
McLachlan G et al., Gene Ther. 2011 Oct;18(10):996-1005. doi: 10.1038/gt.2011.55. Epub 2011 Apr 21.
Electroporation enhances reporter gene expression following delivery of naked plasmid DNA to the lung.
Pringle IA et al., J Gene Med. 2007 May;9(5):369-80.
Human-specific cystic fibrosis transmembrane conductance regulator antibodies detect in vivo gene transfer to ovine airways.
Davidson H et al., Am J Respir Cell Mol Biol. 2006 Jul;35(1):72-83. Epub 2006 Feb 23.
Validation of recombinant Sendai virus in a non-natural host model.
Griesenbach U et al., Gene Ther. 2011 Feb;18(2):182-8. doi: 10.1038/gt.2010.131. Epub 2010 Oct 21.
Plasmid DNA molecules complexed with cationic liposomes are protected from degradation by nucleases and shearing by aerosolisation.
Crook K et al., Gene Ther. 1996 Sep;3(9):834-9.
Enhanced lung gene expression after aerosol delivery of concentrated pDNA/PEI complexes.
Davies LA et al., Mol Ther. 2008 Jul;16(7):1283-90. doi: 10.1038/mt.2008.96. Epub 2008 May 20.
Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis.
Porteous DJ et al., Gene Ther. 1997 Mar;4(3):210-8.
Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy.
Davies LA et al., Hum Gene Ther Clin Dev. 2014 Jun;25(2):97-107. doi: 10.1089/humc.2014.019. Epub 2014 May 27.
pSURF-2, a modified BAC vector for selective YAC cloning and functional analysis.
Boyd AC et al., Biotechniques. 1999 Jul;27(1):164-70, 172, 175.
An immunocytochemical assay to detect human CFTR expression following gene transfer.
Davidson H et al., Mol Cell Probes. 2009 Dec;23(6):272-80. doi: 10.1016/j.mcp.2009.07.001. Epub 2009 Jul 15.
Insertion of natural intron 6a-6b into a human cDNA-derived gene therapy vector for cystic fibrosis improves plasmid stability and permits facile RNA/DNA discrimination.
Boyd AC et al., J Gene Med. 1999 Sep-Oct;1(5):312-21.
Transfection efficiency and toxicity following delivery of naked plasmid DNA and cationic lipid-DNA complexes to ovine lung segments.
Emerson M et al., Mol Ther. 2003 Oct;8(4):646-53.
Measurement of halide efflux from cultured and primary airway epithelial cells using fluorescence indicators.
Munkonge FM et al., J Cyst Fibros. 2004 Aug;3 Suppl 2:171-6.
Toxicology study assessing efficacy and safety of repeated administration of lipid/DNA complexes to mouse lung.
Alton EW et al., Gene Ther. 2014 Jan;21(1):89-95. doi: 10.1038/gt.2013.61. Epub 2013 Nov 7.
The safety profile of a cationic lipid-mediated cystic fibrosis gene transfer agent following repeated monthly aerosol administration to sheep.
Alton EW et al., Biomaterials. 2013 Dec;34(38):10267-77. doi: 10.1016/j.biomaterials.2013.09.023. Epub 2013 Oct 3.
Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis
Alton EW et al., Thorax. 2017 Feb;72(2):137-147. doi: 10.1136/thoraxjnl-2016-208406.
Secreted Gaussia luciferase as a sensitive reporter gene for in vivo and ex vivo studies of airway gene transfer.
Griesenbach U et al., Biomaterials. 2011 Apr;32(10):2614-24. doi: 10.1016/j.biomaterials.2010.12.001. Epub 2011 Jan 15.
A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis.
Alton EW et al., Efficacy and Mechanism Evaluation (2016) Volume: 3 Issue: 5
Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.
Alton EW et al., Lancet Respir Med. 2015 Sep;3(9):684-91. doi: 10.1016/S2213-2600(15)00245-3. Epub 2015 Jul 3.
Persistent Gene Expression in the Ovine Lung from a Human Elongation Factor 1 Alpha Promoter Plasmid Following Non-Viral Gene Delivery.
McLachlan G et al.,The American Society of Gene Therapy Annual Conference (2007)
Repeat Aerosol Delivery of Concentrated PEI/pDNA to the Sheep Lung.
McLachlan G et al.,The American Society of Gene and Cell Therapy Annual Conference (2010)
Delivery of host targeted miRNA therapeutics for the treatment of respiratory viral infections.
McLachlan G et al.,The British Society of Gene Therapy Annual Conference (2015)
Aerosol Delivery of Concentrated pDNA/PEI Formulations to the Sheep Lung.
Davies LA et al.,The American Society of Gene Therapy Annual Conference (2007)
Duration of Reporter Gene Expression from Naked pDNA in the Mouse Lung following Direct Electroporation and Development of Wire Electrodes for Sheep Lung Electroporation Studies.
Pringle IA et al.,The American Society of Gene Therapy Annual Conference (2004)
Quantifying non-viral gene transfer by real-time PCR: a cautionary tale.
Coles R et al.,The European Society of Gene and Cell Therapy Conference (2009)
Aerosol Characteristics of DNA/lipid Formulations for Gene Therapy Clinical Studies.
Gill DR et al.,The North American Cystic Fibrosis Conference (2008)
Optimisation of Aerosol Delivery of Lipid/DNA Complexes for Clinical Studies.
Davies LA et al.,The American Society of Gene Therapy Annual Conference (2008)
3-Step TaqMan RT-PCR: Ultimate mRNA Detection Sensitivity For CF Gene Therapy Clinical Trials.
McCormick D et al.,The North American Cystic Fibrosis Conference (2009)
Optimisation of molecular assays for clinical trial of GL67A/pGM169 delivery to nose and lung of CF patients.
Sumner-Jones SG et al.,The North American Cystic Fibrosis Conference (2009)
CpG depletion results in increased duration of gene expression from plasmid DNA vectors in vivo.
Lawton AE et al.,British Society of Gene Therapy Conference (2006)
Optimising Harvest of Bronchial Brush Biopsy Samples To Maximise Cell and RNA Yield in Gene Therapy Studies.
Vrettou C et al.,The American Society of Gene Therapy Annual Conference (2009)
Near-Single Copy mRNA Quantification from a TaqMan RT-PCR Assay for an Aerosol Gene Therapy Clinical Trial.
Sumner-Jones SG et al.,The American Society of Gene Therapy Annual Conference (2008)
Development of highly sensitive TaqMan RT-PCR assays for quantifying vector mRNA in human samples.
Sumner-Jones SG et al.,The British Society of Gene Therapy Annual Conference (2008)
Repeat Administration of Gl67A/pGM169 Is Feasible, Safe, and Produces Endogenous Levels of CFTR Expression After 12 Doses.
Alton EW et al.,British Thoracic Society Winter Meeting (2012)
Calculating the percentage of cells transfected following non-viral delivery to the respiratory epithelium.
Pringle IA et al.,The American Society of Gene Therapy Annual Conference (2009)
Development of an optimal F/HN pseudotyped SIV vector for CF gene therapy.
Hyde SC et al.,British Thoracic Society Winter Meeting (2014)
Cumulative CFTR expression following repeated aerosol delivery of non-viral pGM169/GL67A formulation to mouse lung.
Sumner-Jones SG et al.,The European Society of Gene and Cell Therapy (2012)
Secreted Gaussia Luciferase Is a More Sensitive Reporter Than Firefly Luciferase for Non- Viral Gene Transfer to Airway Epithelium Ex Vivo and In Vivo.
Griesenbach U et al.,The American Society of Gene Therapy Annual Conference (2009)
Moving lentiviral-based gene therapy into a first-in-man CF trial.
Griesenbach U et al.,The North American Cystic Fibrosis Conference (2015)
Bacterial Lysate (2009): Neutralisation of a bacterial lysate.
DNA fragments being cut from an agarose gel exposed to UV.
Schematic diagram of the large human airways.
Proposed 3D model of the CFTR protein.
Light microscope image of a human airway liquid interface cultures. Dark patches are mucous.
Mouse lung large airway (cell nuclei blue) transduced with an adenoviral vector (green).
A CFTR Western blot, to confirm protein production in cell culture.
Large scale lentivirus production in suspension culture.