The exciting field of small RNA research was the subject of the 2006 Nobel Prize in Medicine, and holds great potential in the diagnosis and prognosis of disease such as cancer. Recent clinical studies suggest that drugs inhibiting small RNAs called microRNA present novel therapeutic opportunities. By defining the non-specific effects of such drugs and investigating new avenues for their delivery, this project will secure the safe application of these drugs into the clinic.
Identification And Evaluation Of Novel Epigenetic Targets For The Treatment Of ? Haemoglobin Disorders
Funder
National Health and Medical Research Council
Funding Amount
$740,809.00
Summary
Symptoms of ?-haemoglobin disorders appear after birth, when fetal haemoglobin (HbF) is replaced by aberrant adult haemoglobin (HbA). Interestingly, the persistent expression of HbF in patients reduces disease severity. This observation has created much interest in understanding the fetal to adult transition, since reversing it can benefit patients. Epigenetics plays a central role to this mechanism. Identifying components of this switch will form the basis of next generation therapies.
Development Of Novel Gene Therapy Vectors For Thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$287,307.00
Summary
Thalassaemia, is a common inherited disorder affecting haemoglobin synthesis. Synthesis of ?/?-globin chain is balanced during normal red blood cell production. Any disruption in the ratio of ?/?-globin chain results in anaemia. In this study, we will explore gene therapy strategies to restore balanced ?:? globin expression and ultimately improve the severely anaemic phenotype in ?-thalassaemia patients.
Thalassaemia, is a common inherited disorder affecting haemoglobin synthesis. Synthesis of ?/?-globin chain is balanced during normal red blood cell production. Any disruption in the ratio of ?/?-globin chain results in anaemia. In this study, we will explore gene therapy strategies to restore balanced ?:? globin expression and ultimately improve the severely anaemic phenotype in ?-thalassaemia patients.
Development Of A Novel Hybrid RAAV/transposon Gene Delivery System For Life-long Correction Of Metabolic Liver Disease In Infants And Children
Funder
National Health and Medical Research Council
Funding Amount
$505,897.00
Summary
The immense potential of gene therapy for the treatment of genetic liver disease has been confirmed by recent success in a clinical trial for Haemophilia in adult males, and therapeutic benefit in other adult trials is imminent using the same technology. In the young, however, ongoing growth of the liver causes the therapeutic benefit to be short-lived. To address this problem we are developing a powerful new hybrid technology capable of conferring life-long benefit on infants and children.
Hepatocellular Carcinoma: Understanding The Genotoxic Risks Of Liver-targeted Gene Therapy Using Recombinant AAV Vectors
Funder
National Health and Medical Research Council
Funding Amount
$891,639.00
Summary
Advances in gene transfer technology using an engineered virus known as AAV underpin success in the treatment of haemophila B, and offer the exciting prospect of treating many other liver diseases. While continued improvement of gene transfer efficiency is essential there is an equal need to focus on safety. We have discovered a genetic element in AAV that we believe is a key to unlocking accurate analysis of the safety of AAV-based gene transfer technology. Here we propose to turn the key.
Directed Evolution Of AAV Capsid Variants For Enhanced Targeted Genome Editing In The Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$386,012.00
Summary
Liver transplantation is often the only treatment option available for patients with severe liver disease, and is complicated by a shortage of donor organs and the need for life-long drug therapy to prevent rejection. Repair of a patient’s own liver by gene therapy is a promising alternative. This project focuses on developing the technology required to undertake precise correction of genetic spelling errors in diseased liver cells without the need to first remove them from the body.
Mechanically-restricted Percutaneous Gene Therapeutic Solutions For Heart Failure.
Funder
National Health and Medical Research Council
Funding Amount
$187,000.00
Summary
We have developed a novel system for the localized delivery of specialised genes to the heart in order to improve contractility and function of a failing heart. Many genes, for reasons of toxicity, clearance, or uptake, require direct delivery to the target region without spillover to the systemic circulation. Our system addresses these issues by isolating the local circulation of the target organ and directly delivering the agent with minimal systemic loss and improved delivery and uptake effic ....We have developed a novel system for the localized delivery of specialised genes to the heart in order to improve contractility and function of a failing heart. Many genes, for reasons of toxicity, clearance, or uptake, require direct delivery to the target region without spillover to the systemic circulation. Our system addresses these issues by isolating the local circulation of the target organ and directly delivering the agent with minimal systemic loss and improved delivery and uptake efficiency, while minimizing potentially dangerous and toxic systemic effects.Read moreRead less
Applying Gene Therapy Towards Limb Girdle Muscular Dystrophy 2I And Other Human Muscle Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$347,264.00
Summary
Therapeutic replacement of small, normal sections of the dystrophin gene can prevent muscle wasting in young dystrophic mice with mutations in dystrophin. This project attempts to apply the same principle to treat another inherited muscle disorder, caused by mutations in the FKRP gene. This approach can also potentially be used to enhance muscle regeneration and treat age related muscle atrophy, or synergistically applied with other therapies that target specific genetic mutations.