Student opportunities
Revolutionising eye disease treatment with next-generation gene therapy
This research project position is open to expressions of interest from PhD students.
Project title: Revolutionising eye disease treatment with next-generation gene therapy
Supervisors: Dr Jiang-Hui (Sloan) Wang and Associate Professor Guei-Sheung (Rick) Liu
Email: sloan.wang@unimelb.edu.au
Suitable for: PhD
Scholarship
Successful applicants will receive a Centre for Eye Research (CERA) PhD Stipend Scholarship to support PhD research studies for this project at CERA. This prestigious award includes a living allowance stipend of $38,500 per annum (2025 rate) equivalent to the Melbourne Research Scholarship (University of Melbourne).
- Applications open – 15 May 2025
- Applications close – 15 May 2026
- Project start date (anticipated) – 1 January 2026
Current retinal gene therapies using adeno-associated viruses (AAVs) require invasive eye injections (subretinal) that risk retinal detachment, limiting treatment effectiveness. A safer, simpler alternative (intravitreal injection) mostly targets the inner retina due to a barrier (inner limiting membrane) trapping viruses via heparan sulfate (HS) binding.
Engineered viruses like AAV2.7m8 reduce HS binding and improve photoreceptor targeting in mice but remain ineffective in primates, suggesting HS reduction alone is insufficient. Challenges include poor retinal penetration, immune reactions, inconsistent tissue targeting, species differences and durability.
This PhD project aims to develop engineered AAV capsid variants capable of efficient photoreceptor transduction via intravitreal injection. Building on a novel capsid screening platform, the project will focus on designing variants that combine reduced heparan sulfate (HS) binding with enhanced affinity for photoreceptor-specific surface proteins.
The central hypothesis is that dual-targeted capsids will overcome current limitations in retinal gene delivery – such as restricted retinal penetration and species-specific variability – by facilitating more efficient and broadly translatable photoreceptor targeting.
The project will pursue two specific aims:
- Engineer AAV2 capsids with both reduced HS binding and robust binding to photoreceptor-specific surface proteins.
- Validate the transduction efficacy of the novel variants in human retinal organoids as well as in vivo models, including both small and large animals.