Developing treatments that can correct the underlying cause of CF is an important goal for the CF research community. One of the areas of research that may deliver this in the future is gene editing. The aim is to edit the CF gene itself, to overcome the damage caused by specific CF mutations. The approach offers the promise of being able to correct all forms of CF, irrespective of which mutations people with CF may have.
While traditional approaches for designing new drugs have been around for centuries, modern gene editing approaches have barely been with us a decade, so there’s a lot to work out. This ranges from how to apply the latest developments in editing the gene itself, to practical obstacles like how to deliver the new therapy, which type of lung cell to deliver it to, investigating potential side effects and, of course, whether it is likely to work.
In this Strategic Research Centre, Professor Stephen Hart at the UCL Great Ormond Street Institute of Child Health, in London, has teamed up with researchers across Europe to apply their expertise in gene editing to cystic fibrosis. They’ll be doing lab testing on gene editing therapy approaches that may be feasible for people with CF in the future.
This project is jointly funded by the Cystic Fibrosis Trust and by the Cystic Fibrosis Foundation in the United States.
Aims of the project in more detail:
Best gene editing tools for the job.
The development of gene editing techniques has been revolutionised by the discovery of a biological tool called CRISPR, reflected in the fact that the two women scientists, who developed it,Jennifer Doudna and Emmanuelle Charpentier, were awarded the Nobel Prize for Chemistry in 2020. The development of new, more sophisticated ways to use CRISPR is a fast-moving area of research. The aim of this programme within the SRC is to work out which CRISPR technique is the most effective for correcting different types of mutations within the CF gene.
Delivering the gene editing tools.
Once the right CRISPR method to correct a specific CF gene has been worked out, the next job is to deliver all the tools that are needed to do the gene editing into lung cells. The SRC team will apply the latest approaches to package and delivering different components of the CRISPR system within the cell.
Delivering gene editing-corrected cells.
As an alternative to delivering the gene editing tools to do ‘on site’ repairs within the lung cells, researchers within the SRC will also develop methods for delivering already-corrected cells into the lungs and incorporating the new cells into the lining of the lungs.
Testing the effectiveness of the gene editing.
Within this aim, the researchers will investigate which type of lung cell to edit, whether the gene editing has restored the function of the CF protein within the cells, and what proportion of cells need to be corrected to restore the lining of the lungs to normal.
Testing gene editing using animal models of cystic fibrosis.
Most of the studies within this SRC will be conducted in cells grown in isolation in dishes in the laboratory. In order to move towards gene editing therapies, the researchers will use animal models of CF to test the delivery, gene-editing and post-editing function of the lung cells.
Who is involved?
Lead Principal Investigator (PI): Professor Stephen Hart, UCL Great Ormond Street Institute of Child Health, London
- Professor Deborah Baines, St George’s University of London
- Dr Paola Bonfanti, The Francis Crick Institute, London
- Dr Patrick Harrison, University College Cork
- Professor Isabelle Sermet-Gaudelus, Necker Enfant-Malades Institute, Paris