Understanding the genetics of cystic fibrosis
On the surface of each and every cell in a healthy lung there are proteins that form channels through which salt and water can pass. These proteins regulate how much of these substances enter and leave the cells to keep it functioning properly. The cystic fibrosis genetic mutations mean that the cells have an error in their instructions (in this case, the CFTR gene), so the protein is not made properly, or is not sent to the cell surface where it is needed. This causes many of the problems you can read about on our How CF affects the body webpage.
How could genetic medicines help people with cystic fibrosis?
The simple answer is that it can correct the mistake in the gene in the cells so that they can make this protein properly and direct it to the cell surface where it is needed.
What’s the difference between gene therapy and gene editing?
Gene therapy includes techniques such as inserting an extra copy of a healthy gene into a cell to replace the faulty gene.
Gene editing, on the other hand, fixes the error in the gene in the cell using specially designed enzymes, called nucleases, which act like molecular scissors.
What are we doing about it?
The Cystic Fibrosis Trust is funding a £750,000 world-class Strategic Research Centre exploring using gene editing to create a new treatment that will fix the mutation that causes the build-up of mucus in the lungs.
We funded the UK Gene Therapy Consortium (GTC) to develop a gene therapy product with the potential to 'correct' the faulty cystic fibrosis gene in the lungs. The GTC announced results from the Phase 2B clinical trials of its Wave 1 gene therapy product in 2015. The next step will be to take the product to Phase 3 trials, the cost of which can be in excess of £100million. Because the Trust cannot afford to fund this research itself, it is likely that a pharmaceutical partner will be sought.
The Trust is also funding a project led by Professor Patrick Harrison exploring the next generation CFTR gene repair. This project is investigating the permanent correction of more than 80% of mutations causing disease in human cystic fibrosis cells.
Other research we are funding includes two exploratory studies into gene editing techniques, and we co-funded a study with Action Medical Research into a non-CFTR approach to gene editing, which has recently finished.
We have also made a submission to a Parliamentary inquiry on genomics and genetic editing in order to ensure the interests of the CF community are at the heart of this vital debate and to raise awareness of the research we are doing in this area.
Why is genome editing so controversial?
There are many different technologies looking at how to fix errors in the human genetic code. Some of these are very controversial and involve the use of embryonic stem cells (cells from human embryos that often have the ability to be turned into any cell type).
Our research does not use these methods, but instead looks at fixing the error in cells that already exist within an individual’s body, for example within the lungs. This does not change the person’s whole genome, as their egg or sperm cells would still carry the CF-causing mutation, but the cells that are treated will then divide to form new, healthy cells that benefit that individual.