NSW-RRTN PhD Scholarship: Development of Fluorescent Janus Dendrimer Nanocarriers for RNA-Based Glaucoma Therapy

Project Impact

RNA-based therapeutics have the potential to enhance patient outcomes by delivering neuroprotective factors (e.g., BDNF via mRNA) or silencing disease-driving genes. However, safe and effective non-viral delivery to retinal neurons remains a major barrier to clinical translation. This project addresses this barrier through a fundamentally new molecular design: a Janus dendrimer that combines delivery, biocompatibility, and built-in imaging in a single architecture.

Supervisory Team

• Principal Supervisor: Dr Nitin Chitranshi, School of Science & Technology, UNE
• Co-Supervisor: A/Prof Kirstan Vessey, School of Science & Technology, UNE
• Co-Supervisor: Dr Brendan Wilkinson, School of Science & Technology, UNE
• External Co-Supervisor: TBC (RRTN partner institution)

Project Description

Glaucoma is the leading cause of irreversible blindness worldwide, affecting over 80 million people including 300,000. The incidence of glaucoma is expected to increase with our aging population. While current treatments focus on lowering intraocular pressure (IOP), they do not address the progressive loss of retinal ganglion cells (RGCs), the neurons whose death ultimately causes vision loss. RNA-based therapeutics offer a powerful new approach to directly protect and potentially rescue RGCs. However, delivering RNA safely and efficiently to the posterior segment of the eye remains a critical unmet challenge.

This project will develop a novel class of fluorescent nanocarrier based on a Janus dendrimer (JD) architecture, which integrates RNA delivery, endosomal escape, and intrinsic imaging capability into a single molecular architecture. Specifically, the project will entail the synthesis of trehalose-histidine hybrid nanocarriers for combined intraocular delivery and fluorescent bioimaging.  A fluorescent PDI core will enable real-time tracking of the nanocarrier using confocal microscopy without the need for external fluorescent labels.

The PhD candidate will synthesize, characterise and perform biological delivery experiments including:

• Design and production of PDI-cored Janus dendrimers bearing trehalose and polyhistidine functionalities, optimising the molecular architecture for self-assembly, RNA binding, and biocompatibility and characterise these dendrimer formulations, especially RNA encapsulation and release.
• Image cellular uptake and intracellular trafficking in RGC and trabecular meshwork cell models using confocal microscopy, exploiting the intrinsic PDI fluorescence to track endosomal escape and cell-type selectivity and assess neuroprotective or gene-silencing efficacy of RNA-loaded dendrimers in glaucoma-relevant in vitro models.
• Evaluate biocompatibility and retinal cell tolerance of dendrimer formulations across a range of concentrations in RGC and retinal pigment epithelium (RPE) cell models, assessing cytotoxicity, inflammatory markers, and cell viability and assess retinal penetration and distribution of fluorescent dendrimers in ex vivo retinal tissue models using confocal imaging

This interdisciplinary project spans synthetic chemistry, nanomaterial science, cell biology, and ocular pharmacology, and will equip the candidate with skills directly translatable to the growing RNA therapeutics sector. The candidate will undertake a 3-month industry internship with a pharmaceutical or biotechnology partner, ensuring exposure to the translational pipeline for RNA therapeutics.