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3 - Cystic fibrosis: the quest for a cure page 5
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3. The quest for a cure Link to the Medical Research Council web site
Gene therapy
Thanks to a world-wide research effort and the elegant techniques of genetic engineering, there are now exciting prospects for the treatment of CF. Rather than merely managing the disease, gene therapy could provide a cure.
Figure 6

Figure 7. Duncan Geddes at the Royal Brompton Hospital in London.
The idea is to smuggle healthy copies of the CF gene into the epithelial cells lining the airways of the lungs. Fortunately, these cells are accessible and can be treated in situ, that is, without removing the cells from the body. The cells would then synthesise correctly-functioning versions of the CFTR protein, resulting in a normal flow of chloride ions and water across the membranes.
  The development of gene therapy for CF depends upon many hours of basic research. Before human trials can begin, techniques are tried and tested in isolated cell cultures and then, if possible, in laboratory animals as a model system.
  What has been achieved so far?
  • Healthy copies of the CF gene have been isolated, inserted into a bacterium and cloned to produce vast numbers of identical copies of the gene for use as experimental material.

  • Systems have been developed for transfer of the healthy CF gene into the DNA of target epithelial cells. Such systems are called vectors.

Figure 8. A bacterial plasmid (a circular double strand of DNA) is sliced to allow a healthy CF gene to be inserted. The doctored strand is negatively charged and is attracted onto the positively charged surface of a liposome. This liposome/DNA complex passes through the cell membrane into an epithelial cell. Here the DNA is transported into the nucleus where the healthy CF gene codes for CFTR synthesis.

Getting the gene where it's wanted

  A number of research teams are using a viral vector to deliver the gene to the epithelial cells. The healthy CF gene is inserted into an adenovirus, which has previously been treated to disable its virulence.

Duncan Geddes and his collaborators in the UK have favoured the use of liposomes as vectors for the CF gene. Liposomes are tiny spheres of lipid molecules which pass easily through cell membranes. Figure 8 shows the method they used.

Both virus and liposome systems have been used successfully to transfer healthy CF genes into cultured human epithelial cells. Also, crucially important to the whole CF research effort was the work carried out using mice with artificially induced CF. Researchers showed that liposomes could transfer the human CF gene safely and effectively into the lung epithelial cells of a living animal. The next step was to do the same thing with humans.

Human trials
Human trials with CF gene therapy demand careful planning and are subject to rigorous control and monitoring. Safety for the patient is of paramount importance. A major programme of research trials is under way in the USA and Europe.
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