Expanding the genome editing toolkit for the treatment of genetic liver disease in children

‘Expanding the genome editing toolkit: evaluating novel gene editing strategies for the treatment of genetic liver disease in children’ research project will test a new genome editing tool called seekRNA to see if it can treat a urea cycle disorder known as ornithine transcarbamylase (OTC) deficiency. It will also explore the potential of seekRNA as a model approach for treating genetic and metabolic liver diseases more broadly”.

Developed by Siddiquee and colleagues in 2024, seekRNA is an advanced gene-editing tool that can introduce DNA into the genome of a target  cell with a high degree of precision.

The major objective of this project is to determine whether the seekRNA gene editing system can be used to correct the metabolic phenotype in OTC deficiency. We are seeking to achieve this by combining our expertise in gene therapy, genome editing, and highly efficient vector systems for delivering genes into the body in combination with the seekRNA technology.

Ornithine transcarbamylase (OTC) deficiency is a genetic liver disorder caused by a deficiency in the OTC enzyme. This enzyme is an essential component of the urea cycle, a metabolic pathway in the liver that removes excess nitrogen from the body. If this pathway is defective, it can lead to the toxic buildup of ammonia in the blood, known as hyperammonemia, which is neurotoxic and can cause brain damage.

While the disorder is rare, affecting an estimated 1 in 14,000 to 1 in 80,000 people, in newborns it can be serious and even life-threatening if untreated, especially for boys.

“OTC deficiency is the most prevalent of the urea cycle disorders. It is also a challenging target because we need to correct a high percentate of liver cells for therapeutic benefit. Therefore, if we can achieve this for OTC deficiency, the same approach will be a viable treatment strategy for many other liver diseases”, says the Lead Investigator, A/Prof Ginn.

Researchers will use seekRNA gene editing technology to restore normal gene function, and to explore the technology for its potential use in patients.

This new research is a continuation of  former research Curing Genetic Liver Diseased by Precise  Genomic and Epigenomic Editing also conducted by Associate Professor Samantha Gin and supported by Luminesce Alliance.