Lead Researcher – Dr Deborah Gill
Establishment – University of Oxford
Dr Deborah Gill provides an update on her research study and what it means for the future of treating childhood liver disease.
We aim to treat paediatric liver diseases caused by genetic mutations (such as alpha-1 antitrypsin deficiency or Wilson’s disease) using gene therapy. Traditional gene therapy approaches deliver a new, functional copy of the gene to liver cells.
This approach is problematic for paediatric liver disease because as the liver grows, and the treated liver cells divide, the new gene is eventually lost. Instead, we proposed to use genome editing to facilitate the precise insertion of a functional copy of the gene into the DNA of a patient’s liver cells. This approach has the potential for that gene to function for the lifetime of the patient.
The main outcome of this work was the successful establishment of the liver organoid model in our lab for the investigation of liver gene editing and gene therapy approaches to liver disease.
We have demonstrated that our genome editing approach can work in human liver cell lines. We also hope to reproduce this work in small artificial livers (known as liver organoids) and in mouse disease models. This work is important because there is currently no definitive cure for AAT deficiency and many other liver diseases.
Two scientific articles have been published as a result of this study so far.
Funding was also used to breed and characterise two mouse models so that we can combine our genome editing strategy with our viral delivery method. This is ongoing. Ultimately, we aim to assess the efficacy, safety and therapeutic applicability of our genome editing platform for the treatment of paediatric genetic liver diseases.