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Overcoming the barrier to human cardiac gene therapy

University of Sydney

  • Cardiovascular Early-Mid Career Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Associate Professor Eddy Kizana

Project summary

Overcoming the major barrier for gene therapy as a treatment modality for patients with all forms of heart disease.

What is the issue for NSW?

Genes are made of DNA which is the code or blueprint for proteins that make our bodies grow and work. Small changes in the DNA code or the way genes are expressed can have major effects on our health. These changes can be inherited or acquired as we age. In the event that a gene change causes disease then gene therapy may be able to help. Gene therapy is the introduction of genetic material into the cells of a patient to treat a specific disease. The transferred genetic material changes how a protein is produced by the cell. This new genetic material is delivered into the cell using a vector.

Typically, viruses are used as vectors because they have evolved to be very good at making their way into cells during infection. In gene therapy however, their purpose is to insert the new genetic material into the cell. Some types of viruses being used are typically not known to cause disease, such as the one in this proposal. In gene therapy, we often use adeno-associated viruses (AAV) as vectors. AAV is a small virus that isn’t known to cause disease, significantly reducing the chance of a negative side effect.

Gene therapy has had success in the treatment for patients with inherited disorders such as haemophilia and acquired disease such as cancer. Progress in gene therapy for patients with heart disease has been limited despite strong predictions of success from experimental models. Much of this lack of clinical benefit is due to the unexpectedly poor performance of the AAV vector in human hearts.

What does the research aim to do and how?

To overcome this barrier this project will use cutting-edge molecular biology technology and Darwinian-like evolutionary principles to create AAV vectors selected for their ability to efficiently deliver genetic material to human hearts. Success with this project will overcome the major barrier for gene therapy as a treatment modality for patients with all forms of heart disease.

The research team (clinicians and scientists) have access to NSW based technology for vector development and a heart biobank that will make this research internationally unique and competitive. This research strategically aligns with other NSW Health supported initiatives for the development of novel biological therapies for human disease. To accelerate the clinical use of promising vectors, protected findings will be disseminated via academic channels and vectors will be made available to other clinician/researchers world-wide to ensure maximum knowledge translation.