Using Gene editing to cure genetic neurological disorders


This project is an opportunity for a PhD student who is interested in genetic disorders of the brain and who is prepared to work at the cutting edge of technology. Genetic neurological disorders are challenging to treat, let alone cure, due to the complexity of the brain and the barrier imposed by the blood brain barrier. Adeno-associated virus (AAV) technology and CRISPR gene editing tools are a novel system which have the capacity to permanently correct mutated genes back to wild type in neuronal cells.


Dr Wendy Gold

Research Location

Westmead - Kids Research Institute

Program Type



Neurological disorders, affecting the structure and/or function of the brain and spine, collectively number more than 600, and include Parkinson disease and Rett syndrome. Genetic neurological disorders are challenging to treat, let alone cure, due to the complexity of the brain with its elaborate molecular, cellular, and neuronal architecture, especially the barrier imposed by the blood brain barrier.

Adeno-associated virus (AAV) delivery is becoming a very popular tool for gene therapy and currently being used in a number of clinical trials. However, there are a number of fundamental obstacles specific for brain disorders, including delivery of therapeutics across the blood brain barrier, and gene dosage. Improved AAV vectors that can effectively cross the blood brain barrier and target brain cells specifically are required.

CRISPR technology is a powerful new tool that is being used to genetically edit genes. This tool can be used to permanently knock out whole genes or make single nucleotide changes. One of the drawbacks with conventional gene therapy is dosage, as the mutated gene is still transcribed into a protein along with the new wild type copy that has been introduced, with the potential that the mutated protein could interfere with the restorative function of the introduced wild type protein. CRISPR has revolutionised gene therapy and circumnavigated these dosage concerns as it permanently edits the existing mutated copy of the gene thus eliminating the need for the introduction of a wild type copy.

This project will use the most advanced techniques in gene therapy and gene editing to create a neuronal specific AAV vector that can deliver CRISPR gene editing tools into neuronal cells of a Rett syndrome mouse model with the aim of correcting the mutation in the methyl CpG-binding protein 2 (MECP2) gene back to wild type.

In this project we will specifically screen a library of novel AAV vectors that have the potential to be used for gene therapy/gene editing. These vectors will be selected on their capacity to transduce neuronal cells in culture and will also be tested in mice in vivo. The superior vectors will be adapted to contain the CRISPR machinery required for gene editing which will then be tested in primary neuronal cells and ultimately mouse models of neurological disorders, with a particular initial focus being on Rett syndrome, which is caused by mutations in MECP2.

Techniques include gene editing, cloning, PCR, western blotting, mice handling, microscopy, flow cytometry.

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paediatric, neurology, genetic, CRISPR, gene editing, Adeno-associated virus (AAV), Gene therapy

Opportunity ID

The opportunity ID for this research opportunity is: 2253