Only a few years ago, people living with an inherited retinal disease (IRD) were expected to experience gradual vision loss, but new gene therapy technology has the potential to stop these conditions in their tracks.
These therapies need to be taken to the right part of the eye by a delivery vehicle - usually a safe, modified virus called a viral vector.
The adeno-associated virus is a commonly used viral vector, but its limited size means it cannot fit the larger genes associated with many of the 300 other known IRDs.
Treatments for many IRDs will need a different vehicle.
The problem is a little like a large group of passengers needing to get directly to their destination together.
"Some delivery vehicles are a bit like a taxi - they can transport you directly to your destination but will only fit a limited number of passengers," says Dr Sandy Hung, Research Fellow in CERA's Clinical Genetics Unit.
"Whereas others are more like a bus - they can carry more passengers but may take an indirect route and not arrive directly at your destination."
Dr Hung is working to develop ways to ensure larger delivery vehicles can better target specific cells in the light-sensing retina.
"This will help us deliver more treatments to the cells affected in IRDs," she says.
Correcting genes
There are many different types of IRD - each caused by a change or mistake in one or more different genes.
Once the specific genetic mistake is found, researchers like Dr Hung use gene editing tools to try and find a way to correct the mistakes.
"Developments have advanced so fast there are now many new tools that can potentially allow us to correct the genetic 'mistakes' that occur in different IRDs," says Dr Hung.
"However, a current major bottleneck for researchers is the ability to deliver these gene editing tools to the cells that are affected in the retina.
"Now we are going to try and make virus delivery systems with the retinal cell specificity that can also carry larger gene editing systems or large genes."
Different IRDs or genetic mistakes cause different cell types of the retina to not function properly, which can lead to vision loss.
"The first cell type that we're targeting is the photoreceptor cells," says Dr Hung.
Photoreceptors are tiny light-sensing cells that line our retina at the back of the eye, sending messages to our brain which enable us to see.
If successful, the research could potentially benefit people with IRDs such as retinitis pigmentosa.
"While we currently aim to target photoreceptor cells, there is a potential to target other retinal cell types and have an impact on more people with other IRDs," says Dr Hung.
Keeping patients in mind is what motivates Dr Hung to push her research forward.
"From a young age, I wanted to become a scientist as a close family member became ill, and I wanted to help find a treatment," she says.
"Being able to work on projects where the ultimate aim is helping patients is still what motivates me to continue science."
This article first appeared in Visionary magazine – Spring 2023.
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