When it comes to gene therapy, the eye is almost the perfect organ.

As well as being easy to access, eyes are largely isolated from the rest of the body, which means anything introduced into the eye – such as a virus carrying a therapeutic gene – is unlikely to affect other parts of the body.

The extraordinary potential of gene therapy to halt or even reverse vision loss in patients with inherited retinal diseases (IRDs) and common eye diseases is the reason CERA’s Head of Genetic Engineering Research, Associate Professor Guei-Sheung (Rick) Liu, is so passionate about his research.

“Being diagnosed with an IRD, and the prospect of vision loss, is life changing,” Associate Professor Liu says.

“Before the advent of gene therapy, there was virtually nothing doctors could do for people with these devastating eye diseases, but gene therapy brings real hope.’’

IRD improvements

Some eye diseases are caused by a defect in a single gene passed down through family members. These are known as inherited retinal diseases (IRDs), and collectively they are the most common causes of legal blindness in children, young adults and working-age Australians.

Gene therapy functions by introducing normal genes to replace defective genes (gene replacement) or directly correcting genetic mutations on defective genes (gene editing) that are responsible for impairing the function of eye cells.

One key focus of the team is how gene editing can treat IRDs, which include conditions such as retinitis pigmentosa, Usher syndrome and Stargardt’s disease.

In 2023, Dr Liu’s work attracted Ideas Grant funding from the National Health and Medical Research Council (NHMRC).

The funding was for Dr Liu and his team to test a new technology – ‘RNA base editor’ – to correct genetic errors in RNA.

RNA plays an important role in reading the genetic instructions stored in DNA and sending them to the rest of the body.

“Much of the current research into IRDs looks at treatments that focus on gene replacement, using a safe virus to deliver the correct version of the gene to the retina,” Associate Professor Liu says.

“However, about 40 per cent of the diseases cannot be treated in that way, sometimes because they are caused by genes that are too large to fit on the delivery virus.”

Editing RNA is a way to get around this problem.

“Directly correcting the error in the genetic code means we won’t be limited by the size of the mutated gene that causes the disease,” Associate Professor Liu says.

Goodbye, needles

Another promising gene therapy development in Dr Liu’s research is the SwitchGene, which attracted industry funding from Oculus BioMed in 2023.

Patients with conditions such as wet age-related macular degeneration and diabetic retinopathy often need to have frequent, ongoing injections to prevent vision loss.

In collaboration with Oculus BioMed, Dr Liu’s SwitchGene project envisions a single gene therapy injection, enabling the body to produce its own treatment controlled through eye drops.

“Patients now need to have injections into their eyeball perhaps every six to eight weeks, often for a couple of years or even the rest of their lives,” Associate Professor Liu says.

“This can be uncomfortable, risky, and expensive to the healthcare system.

“Our work with Oculus BioMed aims to solve this issue by a novel gene therapy approach.

“No more eye injections needed.”

This story was originally published in People in focus: Annual Review 2023.