Cystic Fibrosis Gene Repair – Less is More?
The gene editing group led by Patrick Harrison has secured two new grants totalling €140,000 from American CF Foundation and UK CF Trust to fund a two-year project to develop CRISPR gene editing for a group of CFTR mutations which affect mRNA splicing.
The group has previously used both ZFN and CRISPR technology to correct the most common CFTR mutation, p.F508del, which affects 70% of CF patients (Lee et al., 2012; Hollywood et al., 2013).
The gene editing team have identified three sets of patients whose CF is caused by the presence of mutant DNA sequences in their genome. By using a simpler but more efficient form of CRISPR editing to excise the these sequences, it should be possible to restore normal cellular function. The gene editing work in Cork will be performed by Dr. David Sanz, an experienced molecular biologist has recently joined the lab from Valladolid, Spain.
In order to quantify restoration of cellular function, the group has teamed up with two leading CF researchers at the University of Dundee, Drs. Anil Mehta and Stephen Land. They have developed state-of-the-art air-liquid interface cultures of primary human lung cells from CF patients which closely mimic their natural environment and have secured an additional grant of €85,000 from the American CF Foundation for this project.
As part of a larger programme to develop novel gene-based therapeutic approaches, the American CF Foundation is hosting a two-day workshop in Washington D.C. where Dr. Harrison has been invited to give a presentation on the CRISPR gene editing strategy.
- Hollywood, JA, Lee, CM, Kaschig, K., Artemiuk, P., Scallan, MFand Harrison, PT (2013). Gene editing of CFTR and CTNS mutations using ZFNs and CRISPR/Cas-9 guide RNAs. Human Gene Therapy 24:(12) A87.
- Lee CM, Flynn R, Hollywood JA, Scallan MF, Harrison PT (2012). Correction of ΔF508 in CFTR Gene by ZFN-HDR. BioResearch Open Access1(3):99-108.
- Patrick Harrison, Physiology, UCC: publish.ucc.ie/researchprofiles/C008/pharrison
- Cystic Fibrosis Foundation, Bethesda, MD, USA: cff.org
- Cystic Fibrosis Trust, Bromley, UK: cysticfibrosis.org.uk