GENE THERAPY FOR GENETIC BONE DISEASES

Summary

Gene therapy is becoming a practical approach to treat severe genetic conditions and in recent years conditions such as Spinal Muscular Atrophy (SMA) have been success stories. Our team has been working on developing approaches that would work for genetic bone conditions such as Osteogenesis Imperfecta (OI). This family of bone fragility disorders vary in severity, but in some cases can lead to perinatal or neonatal lethality. This project will involve building on prior work by our team in developing AAV (adeno-associated viral) vectors that specifically target the bone. The next step in our research is to modify existing viruses in order to use CRISRP-Cas9 approaches to correct simple OI mutations. This work has the potential to be transformation for patients with these devastating conditions.

Supervisor(s)

Associate Professor Aaron Schindeler, Associate Professor Craig Munns

Research Location

Westmead - Kids Research Institute

Program Type

PHD

Synopsis

This project involves the development of custom AAV vectors and their production. Our team has significant experience in this area (https://doi.org/10.1016/j.omtm.2019.08.010) having designed a bone-specific AAV that works in vivo at high specificity. 
In addition to designing new vectors that enable in vivo gene editing using CRIPSR-Cas9, the student will also have the opportunity to using existing AAV8-Sp7-Cre viruses with established conditional mouse models to explore the role of different genes in bone health. This vector will enable gene deletion to be both specific and timed. 
Current strategies for bone gene therapy are often focused on gene repair in vitro (in cells in a dish) and there is a major technical gap to therapy that is rarely talked about. This project is fundamentally translational as it aims to tackle the major hurdle to practical therapies – in vivo gene editing. 
We are seeking motivated students interested in developing their technical skills and keen to work on a project that has considerable therapeutic potential. This project is ideal as a PhD project. A strong candidate will be able to work as part of a multidisciplinary research team and have strong written/oral communication skills. The capacity to attract an independent scholarship (first class honours, prior publications) will be looked upon extremely favourably.

Additional Information

For more information contact A/Prof Aaron Schindeler at aaron.schindeler@sydney.edu.au or +61 2 98451451.  

Keywords

Bone, gene editing, osteoblast, Osteogenesis Imperfecta, Gene therapy

Opportunity ID

The opportunity ID for this research opportunity is: 2868

Other opportunities with Associate Professor Aaron Schindeler

• PRECLINICAL AND CLINICAL DEVELOPMENT OF NOVEL BONE-BINDING ANTIMICROBIALS
• UNDERSTANDING GENETIC VARIATIONS IN BONE

Other opportunities with Associate Professor Craig Munns

• Musculoskeletal Health of Children with Neurofibromatosis Type I
• UNDERSTANDING GENETIC VARIATIONS IN BONE