Cure 4 Cystic Fibrosis aims to find a cure for CF by supporting promising areas of scientific research. To date, this has seen the Foundation support the research being undertaken by the Adelaide CF Airway Gene Therapy Research Group, which is focussed on a gene therapy approach to treat and potentially cure cystic fibrosis (CF) airway disease. If the techniques and strategies being developed by the team are successful, this research has the potential to improve and save the lives of the 3,000 people living with CF in Australia and more than 70,000 people worldwide.
The group employs a world-leading gene transfer approach. They use an especially modified virus to take a correcting gene into the airway, supplementing the defective gene that causes CF airway disease. The cell then takes over the job of producing the normal airway physiology.
The most exciting aspect of the work is that although this approach should produce long term gene therapy treatments, it is also a potential cure for the airway disease in CF. It is designed to correct airway stem cells. This means that as new airway cells are produced by the body they will have the corrected gene operating within them. Success in this research project means that people living with CF airway disease will, for the first time, be able to live well and potentially be free of this disease.
Research undertaken by the team has shown that their gene transfer approach is successful in several animal models. The next challenge is to continue to develop their work to the point where they can commence trials of the gene transfer approach in cystic fibrosis patients.
The research team has made a number of significant advances, particularly around the use of the actual gene transfer approach. Of particular importance was their work that showed the ability of the research team to produce a properly functioning expression of the gene that corrects the cystic fibrosis defect for more than 12 months. No other research group worldwide had been able to attain such extended gene correction.
Select Research Publications
Through the publication of their research the team shares their techniques and developments with the scientific community. Below is a selection of the research publications produced by the team, many of which have been published by highly regarded academic journals.
Morgan, KS, Donnelley, M, Farrow, N, Fouras, A, Yagi, N, Suzuki, Y, Takeuchi, A, Uesugi, K, Boucher, RC, Siu, KKW & Parsons, DW 2014, ‘In vivo x-ray imaging reveals improved airway surface hydration after a therapy designed for Cystic Fibrosis’ American Journal of Respiratory and Critical Care Medicine. In press.
Donnelley M, Morgan KS, Siu KK, Fouras, A, Farrow, NR, Carnibella RP & Parsons DW 2014, ‘Tracking extended mucociliary transport activity of individual deposited particles: longitudinal synchrotron X-ray imaging in live mice’. Journal of Synchrotron Radiation, vol. 21, pt. 4, 768-773.
Summary available at: http://dx.doi.org/10.1107/S160057751400856X
Donnelley, M, Morgan, KS, Siu, KK, Farrow, NR, Stahr, CS, Boucher, RC, Fouras, A & Parsons, DW 2014 ‘Non-invasive airway health assessment: synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo’. Scientific Reports, 4, 3689.
Article available at: http://dx.doi.org/10.1038/srep03689
Morgan, KS, Donnelley, M, Paganin, DM, Fouras, A, Yagi, N, Suzuki, Y, Takeuchi, A, Uesugi, K, Boucher, RC, Parsons, DW & Siu, KK 2013, ‘Measuring airway surface liquid depth in ex vivo mouse airways by x-ray imaging for the assessment of cystic fibrosis airway therapies’. PLoS One vol. 8(1): e55822 (2013).
Article available at: http://dx.doi.org/10.1371/journal.pone.0055822
Farrow, N, Miller, D, Cmielewski, P, Donnelley, M, Bright, R & Parsons, DW 2013, ‘Airway gene transfer in a non-human primate: Lentiviral gene expression in marmoset lungs’. Scientific Reports, 3, 1287.
Article available at: http://dx.doi.org/10.1038/srep01287
Donnelley, M, Morgan, KS, Siu, KK & Parsons, DW 2013, ‘Variability of In Vivo Fluid Dose Distribution in Mouse Airways Is Visualized by High-Speed Synchrotron X-Ray Imaging’, Journal of Aerosol Medicine and Pulmonary Drug Delivery, vol. 26, no. 5, pp. 307-316.
Summary available at: http://dx.doi.org/10.1089/jamp.2012.1007
Donnelley, M, Morgan, KS, Siu, KKW & Parsons, DW 2012, ‘Dry deposition of pollutant and marker particles onto live mouse airway surfaces enhances monitoring of individual particle mucociliary transit behaviour’, Journal of Synchrotron Radiation, vol. 19, no. 4, pp. 551-558.
Summary available at: http://dx.doi.org/10.1107/S0909049512018250
Donnelley, M, Siu, KKW, Jamison, RA & Parsons, DW 2012, ‘Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways’, Gene Therapy, vol. 19, no. 1, pp. 8-14.
Article available at: http://dx.doi.org/10.1038/gt.2011.80
Liu, C, Wong, E, Miller, D, Smith, G, Anson, D & Parsons, D 2010, ‘Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges’, The Journal of Gene Medicine, vol. 12, no. 8, pp. 647-658.
Summary available at: http://onlinelibrary.wiley.com/doi/10.1002/jgm.1481/abstract.
Donnelley, M, Siu, KK, Morgan, KS, Skinner, W, Suzuki, Y, Takeuchi, A, Uesugi, K, Yagi, N & Parsons, DW 2010, ‘A new technique to examine individual pollutant particle and fibre deposition and transit behaviour in live mouse trachea’, Journal of Synchrotron Radiation, vol. 17, no. 6, Nov, pp. 719-729.
Article available at: http://scripts.iucr.org/cgi-bin/paper?S0909049510028451.
Donnelley, M, Parsons, D, Morgan, K & Siu, K 2010, ‘Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging’, AIP Conference Proceedings, vol. 1266, no. 1, pp. 30-34.
Summary available at: http://link.aip.org/link/?APCPCS/1266/30/1
Cmielewski, P, Anson, DS & Parsons, DW 2010, ‘Lysophosphatidylcholine as an adjuvant for lentiviral vector mediated gene transfer to airway epithelium: effect of acyl chain length’, Respiratory Research, vol. 11, p. 84.
Article available at: http://respiratory-research.com/content/11/1/84.