Understanding immune responses to retinal gene therapy
Dr Colin Chu | GR001504
21 November 2023
We are funding a PhD studentship, supervised by Dr Colin Chu and Professor Andrew Dick, to investigate how the immune system responds to eye gene therapy.
The challenge
Gene therapy is a promising and rapidly growing approach for treating inherited retinal diseases.
Eye inflammation can be a side effect of gene therapy and trigger progressive retinal damage and loss of visual function.
These side effects have been reported with Luxturna®, the first licensed retinal gene therapy.
What is gene therapy?
Learn more
- Gene therapy is a novel technique using genes to treat or prevent disease. It allows doctors to insert healthy versions of genes into patient’s cells to replace faulty, defective or missing genes and restore their function.
- Healthy genes are packaged into harmless viruses, or vectors, and delivered into the target cells by surgery. The viruses are modified so they cannot cause disease.
- Luxturna® is a gene therapy that contains the active biologic voretigene neparvovec. It was approved in 2017 and successfully used to treat adults and children with vision loss due to rare inherited retinal dystrophies.
- Luxturna® targets mutations in the gene RPE65, delivering a healthy version of the gene to the retina to improve vision. It was used to treat patients with retinitis pigmentosa due to mutation in RPE65 and Leber’s congenital amaurosis.
How the immune system responds to gene therapy is poorly understood and appears to be affected by the dose, route, transferred gene and how it is packaged.
Further work is needed to model inflammation and study the immune responses to gene therapy observed in some patients.
Finding a solution
Dr Chu and team are using a recently developed imaging technology called multiplexed immunohistochemistry and Thunder microscope, funded by Moorfields Eye Charity, to look at the cell types involved and the markers of inflammation in the retina.
This will allow them to understand the underlying processes of the immune responses to gene therapy.
Dr Colin Chu working in a lab at the UCL Institute of Ophthalmology
The PhD student, Rose Avient, will learn and apply cutting-edge imaging technologies to study these responses in the eye.
She will investigate the dynamic interactions between immune cells and retinal cells.
She will examine the effects of gene therapy dose and route of administration and test different modifying treatments, including steroids and antibody injections, to dampen the immune response partially.
The potential
This PhD project aims to understand better and find ways to modulate and minimise immune responses to gene therapy. The information would be of direct translational relevance to ongoing clinical trials.
The results could help inform the management of patients who have already received eye gene therapy and understand what may be happening and what approaches might be needed.
Rose Avient, PhD student at the UCL Institute of Ophthalmology
“I’m excited to start my PhD and use cutting-edge technologies to understand the immune responses to adeno-associated viral vectors, as I believe this will be an important step in developing better gene therapies.”
Rose
The detailed data obtained using this technology will advance the understanding of immune responses in the eye. This will inform the development and administration of future gene therapies.
Project Details
PhD studentship
Dr Colin Chu and Professor Andrew Dick
Eye inflammation, Gene therapy
£124,270
October 2023
GR001504
