What is the issue for NSW?
Gene therapies based on adeno-associated virus are beginning to transform the lives of patients living with rare diseases. This is largely through advancement of the technology for more efficient gene delivery. However, a significant obstacle to the application of the therapies is the presence in some patients of pre-existing immunity to the adeno-associated virus delivery system that neutralises therapeutic benefit and precludes treatment. The incidence of immunity, specifically anti- adeno-associated virus antibodies, increases overtime from birth and is acquired by natural exposure to the parent virus circulating in the community. Strategies need to be developed to overcome this obstacle for the wider adoption and equitable application of this transformative technology.
What does the research aim to do and how?
This project aims to develop novel “cloaking” molecules that will bind the surface of the adeno-associated virus gene therapy systems to protect the therapy from neutralisation by human anti-AAV antibodies. The molecules will be “naturally selected” from complex libraries of designed ankyrin repeat proteins (DARPins) to bind critical regions on the adeno-associated virus surface to prevent antibody neutralisation whilst preserving vector function. This “cloaking” strategy will provide access to therapy for patients who would otherwise be precluded from the transformative technology because of pre-existing immunity to adeno-associated virus.