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
Research Assistant in Genome Editing and Gene Therapy (Oxford)
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
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.
Revisiting the mouse lung model for CF.
Boyd AC et al., Gene Ther. 2004 May;11(9):737-8.
The effects of plasmid copy number and sequence context upon transfection efficiency.
Walker WE et al., J Control Release. 2004 Jan 8;94(1):245-52.
PCR-generated cross-over linkers for site-directed mutagenesis.
Boyd AC et al., Biotechniques. 1997 Nov;23(5):827-30.
A Phase I/IIa Safety and Efficacy Study of Nebulized Liposome-mediated Gene Therapy for Cystic Fibrosis Supports a Multidose Trial.
Alton EW et al., AJRCCM, Volume 192, Pages 1389-1392
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.
HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes.
Hyndman L et al., J Control Release. 2004 Oct 19;99(3):435-44.
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.
Potent stimulation of gene expression by histone deacetylase inhibitors on transiently transfected DNA.
Nan X et al., Biochem Biophys Res Commun. 2004 Nov 5;324(1):348-54.
Genomic sequence analysis of Fugu rubripes CFTR and flanking genes in a 60 kb region conserving synteny with 800 kb of human chromosome 7.
Davidson H et al., Genome Res. 2000 Aug;10(8):1194-203.
Elimination of contaminant Escherichia coli chromosomal DNA from preparations of P1 artificial chromosome recombinants facilitates directed subcloning.
Davidson H et al., Electrophoresis. 1999 Jun;20(7):1469-75.
Tripod-like cationic lipids as novel gene carriers.
Unciti-Broceta A et al., J Med Chem. 2008 Jul 24;51(14):4076-84. doi: 10.1021/jm701493f. Epub 2008 Jun 26.
Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis.
Horsley AR et al., Thorax. 2008 Feb;63(2):135-40. Epub 2007 Aug 3.
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.
Towards gene therapy for cystic fibrosis: a clinical progress report.
Alton EW et al., Gene Ther. 1998 Mar;5(3):291-2.
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.
Sputum trace metals are biomarkers of inflammatory and suppurative lung disease.
Gray RD et al., Chest. 2010 Mar;137(3):635-41. doi: 10.1378/chest.09-1047. Epub 2009 Oct 3.
Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR.
Scott-Ward TS et al., Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16365-70. Epub 2007 Oct 3.
Sputum proteomics in inflammatory and suppurative respiratory diseases.
Gray RD et al., Am J Respir Crit Care Med. 2008 Sep 1;178(5):444-52. doi: 10.1164/rccm.200703-409OC. Epub 2008 Jun 19.
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.
Biomarkers for cystic fibrosis lung disease: application of SELDI-TOF mass spectrometry to BAL fluid.
MacGregor G et al., J Cyst Fibros. 2008 Sep;7(5):352-8. doi: 10.1016/j.jcf.2007.12.005. Epub 2008 Feb 1.
Self-reactive CFTR T cells in humans: implications for gene therapy.
Calcedo R et al., Hum Gene Ther Clin Dev. 2013 Sep;24(3):108-15. doi: 10.1089/humc.2012.249. Epub 2013 Jul 19.
SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic obstructive pulmonary disease.
Gomes-Alves P et al., Clin Biochem. 2010 Jan;43(1-2):168-77. doi: 10.1016/j.clinbiochem.2009.10.006. Epub 2009 Oct 20.
A randomised, double-blind, placebo-controlled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis.
Alton EW et al., Thorax. 2013 Nov;68(11):1075-7. doi: 10.1136/thoraxjnl-2013-203309. Epub 2013 Mar 22.
Differential global gene expression in cystic fibrosis nasal and bronchial epithelium.
Ogilvie V et al., Genomics. 2011 Nov;98(5):327-36. doi: 10.1016/j.ygeno.2011.06.008. Epub 2011 Jul 2.
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.
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.
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.
Detection of CFTR transgene mRNA expression in respiratory epithelium isolated from the murine nasal cavity.
Holder E et al., J Gene Med. 2010 Jan;12(1):55-63. doi: 10.1002/jgm.1413.
Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy.
Griesenbach U et al., Am J Respir Crit Care Med. 2012 Nov 1;186(9):846-56. doi: 10.1164/rccm.201206-1056OC. Epub 2012 Sep 6.
CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.
Hyde SC et al., Nat Biotechnol. 2008 May;26(5):549-51. doi: 10.1038/nbt1399. Epub 2008 Apr 27.
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.
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.
Sendai virus-mediated CFTR gene transfer to the airway epithelium.
Ferrari S et al., Gene Ther. 2007 Oct;14(19):1371-9. Epub 2007 Jun 28.
Optimizing aerosol gene delivery and expression in the ovine lung.
McLachlan G et al., Mol Ther. 2007 Feb;15(2):348-54.
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.
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.
Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation.
Horsley AR et al., Thorax. 2013 Jun;68(6):532-9. doi: 10.1136/thoraxjnl-2012-202538. Epub 2013 Feb 9.
Limitations of the murine nose in the development of nonviral airway gene transfer.
Griesenbach U et al., Am J Respir Cell Mol Biol. 2010 Jul;43(1):46-54. doi: 10.1165/rcmb.2009-0075OC. Epub 2009 Jul 31.
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.
Safety and expression of a single dose of lipidmediated CFTR gene therapy to the upper and lower airways of patients with Cystic Fibrosis.
Davies G et al.,British Thoracic Society Winter Meeting (2011)
Longitudinal assessment of biomarkers for clinical trials of novel therapeutic agents: the Run-In study.
Alton EW et al.,British Thoracic Society Winter Meeting (2010)
Mutliple Doses of Lipid Mediated Gene Therapy Nebulised to the Mouse Lung Show Robust and Sustained CFTR Expression.
Hyde SC et al.,The North American Cystic Fibrosis Conference (2011)
Update on the UK CF Gene Therapy Consortium Multidose, Non-viral, Gene Therapy Trial
Alton EW et al.,The North American Cystic Fibrosis Conference (2012)
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)
Assessment of F/HN-Pseudotyped Lentivirus in a Clinically Relevant Vector for Lung Gene Therapy
Griesenbach U et al.,The North American Cystic Fibrosis Conference (2012)
Assessment of FHN-Pseudotyped Lentivirus as a Clinically Relevant Vector For Lung Gene Therapy.
Griesenbach U et al.,British Thoracic Society Winter Meeting (2012)
A randomized, double-blind, placebo-controlled trial of repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis.
Alton EW et al.,The North American Cystic Fibrosis Conference (2015)
Bacterial Lysate (2009): Neutralisation of a bacterial lysate.
E.coli from a large scale industrial production of our clinical trial plasmid pGM169.
Purifying mRNA from tissue samples.
A pellet of E.coli containing a plasmid expressing a pink fluorescent protein.
Proposed 3D model of the CFTR protein.
Pellets of DNA following precipitation.
Light microscope image of a human airway liquid interface cultures. Dark patches are mucous.
Sheep lung parenchyma (cell nuclei blue) transduced with an adenoviral vector (green).
DNA fragments being cut from an agarose gel exposed to UV.
Schematic diagram of the large human airways.