Common genetics terms – what do they mean?
- DNA: DNA is made up of a very long string of nucleotides or 'letters', tightly coiled up in the nucleus of all the cells in your body. Within the long string of letters are the instructions for building and maintaining each cell in the body. The DNA in each cell is called the genome. Each person has slight differences in the string of letters which means that everyone has a unique genome.
- Gene: a gene is a section of DNA that holds the code (or ‘codes for’) a specific protein. There are about 24,000 different genes in humans. Errors in the order of the string of letters of a gene are called mutations, and these can result in a faulty protein or even prevent a protein being made. People with cystic fibrosis are born with an error (or 'mutation') in the cystic fibrosis gene, resulting in a faulty protein.
- Protein: proteins are the building blocks of cells, which in turn make up tissues, and those in turn make up organs in the body.
How does genome editing work?
Genome editing is a way in which mutations in genes can be corrected, therefore allowing cells to make functional protein again.
We are investing in research that uses genome editing to repair the cystic fibrosis mutation in lung cells. The work we fund is investigating the best and safest way to do this in cells from people with cystic fibrosis and other models of disease. Because the work is still experimental, it is not being tested directly in humans.
How is gene editing different to gene therapy?
Gene therapy involves either replacing a faulty gene with a healthy gene or adding a new gene in an attempt to prevent disease. Although promising, at the moment, gene therapy is still experimental and the only way to receive gene therapy would be to participate in an experimental clinical trial. We fund research into gene therapy for cystic fibrosis.
How is gene editing different to Kalydeco or Orkambi?
Kalydeco and Orkambi do not affect the genetic code. Instead, they make the still-faulty protein more able to carry out its function, thereby relieving some of the symptoms of the disease. The beneficial effects disappear when you stop taking the medicine.
What's the potential of gene editing for CF?
Genome editing is still at the experimental stage. The hope is to correct the faulty gene in the cells in the lungs of people with cystic fibrosis. If the gene is corrected, the healthy protein would be produced. This means that the cells would be able to regulate the flow of salt and water in and out, and there will be a reduced build-up of mucus that is less sticky.
How is this being used in other conditions?
Unlike gene therapy, which was discovered decades ago, gene editing is still fairly new. Most research is still experimental. Several clinical experimental trials are planned for this year for people with cancer and results from a genome editing trial for people who are HIV positive have shown promise.
When will it be available?
As with most new treatments it’s very hard to answer. We’re funding preliminary research into making the treatment work, and how to deliver it to the lungs, which can take years, and after this there are very stringent efficacy and safety tests to go through before clinical trials. All in all this could be ten years or more in the future, although we hope to make sure the process of finding a suitable treatment goes as smoothly as possible.
Are we imagining a future where people are no longer born with these conditions?
The research we are funding is aimed at correcting the error in the gene that causes cystic fibrosis, in the laboratory. The researchers are aiming to better understand how clinicians could be able to ‘insert’ this correction to the gene into the cells of the airways of people with cystic fibrosis.
If successfully corrected in these cells, the lungs would function normally and people with cystic fibrosis would be able to clear their lungs more easily and be at much lower risk of dangerous respiratory infections. However, the error will remain in the other cells in the body, meaning that digestive, reproductive and other challenges would persist.
In order for a person to be born without the condition, the gene in all the cells of the body would have to be corrected. The only way to do this is to perform genome editing in an embryo – this type of research has far reaching consequences and is prohibited under UK law. Embryonic stem cell editing is, however, the subject of significant debate in global discussions on potential medical uses. The Cystic Fibrosis Trust is committed to being at the heart of the debate and representing the views of people with cystic fibrosis and their loved ones.
What does the law say?
Gene editing is legal, but highly regulated. You need ethical approval and a license from the Medicine and Healthcare products Regulatory Authority (MHRA) to undertake somatic editing (that is, editing of non-sperm/egg cells, so any subsequent offspring would not inherit the result of these changes). The law prohibits the implantation of genetically altered embryos, with the exception of mitochondrial replacement therapy, which was made legal in the UK in 2015. The entire process - in both a research and clinical setting - is then overseen by the Human Tissue Authority.
What research of this kind is the Trust doing/funding?
The Cystic Fibrosis Trust is funding a £750,000 world-class Strategic Research Centre exploring using gene editing to create a new treatment that aims to fix the mutation that causes the build-up of mucus in the lungs, as well as a VIA that has recently ascertained the best way of delivering this treatment to 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 GTC are currently seeking a pharmaceutical partner to fund Phase 3 trials of the product, for which costs can be in excess of £100million.
The Trust is also funding a project led by Professor Patrick Harrison exploring second 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.
How can I find more info on this?
Visit our page on gene therapy and gene editing, read a feature about our submission to the parliamentary enquiry or take a more detailed look at our SRC on gene editing.