Dr Jiang-Hui (Sloan) Wang is a rising star in eye research and is bringing his cutting-edge gene therapy capabilities back to Australia from the United States.

His new lab at CERA will be one of only a handful in the world capable of developing new viral vectors to treat inherited retinal diseases (IRDs) that involve large genes, like Usher syndrome.

As well as his own projects, Dr Wang’s work is anticipated to help accelerate research across CERA that is aiming to develop gene therapies for several sight-threatening conditions.

Mutations in the MYO7A gene – which direct the making, development and function of photoreceptor cells in the retina – is the major cause of Usher syndrome type 1B.

It leads to profound hearing loss, a progressive decline in vision from teen to adult years and balance problems.

Safer procedures

IRDs that involve large genes like Usher syndrome were once considered untreatable, but gene therapies that can correct faulty genes and prevent vision loss are beginning to emerge.

These therapies often require delicate, invasive injections of harmless viral vectors – known as adeno-associated viruses (AAVs) – to be delivered beneath the retina carrying the corrected gene.

However, there is a limit to how much AAVs can carry.

“The MYO7A gene that causes Usher syndrome is too large for a single AAV to deliver to fix the mutations, and previous attempts to deliver the genes in two AAVs has had mixed results,” says Dr Wang.

Whilst the AAVs themselves are safe, the deep injections that deliver them to the eye have the risk of damaging the very cells that they’re meant to save.

By contrast, the simple eye injections used for common conditions like macular degeneration, are much safer but can’t penetrate deep enough to reach the light sensing cells.

It’s like having a lifesaving medicine that stops at the gate and never gets delivered.

That’s why researchers consider it the ‘holy grail’ to engineer AAVs capable of traversing the eye’s natural barriers via minimally invasive injections.

Greater view

Dr Wang’s revolutionary approach uses a less invasive injection to deliver the full MYO7A gene into the eye.

By splitting the large MYO7A gene and reassembling it inside the retina using a specially engineered AAV vector he developed, his aim is to reverse the effects of retinal disease in a mouse model of Usher syndrome.

Having developed techniques and processes under the mentorship of Professor Guangping Gao at UMass Chan in Massachusetts, United States – one of the world’s leading experts in AAV and gene therapy – Dr Wang is now bringing cutting edge technology back to Australia for further development and eventual clinical use.

Dr Wang is deeply appreciative that his work is being supported by CERA’s community of donors.

“These generous gifts will make a meaningful difference in accelerating our efforts to develop gene therapy for Usher syndrome.

“If successful, this method could offer a safe and efficient way to treat other inherited retinal diseases with large genes, using the same injection approach, and will benefit teams working to develop gene therapies across CERA, including Associate Professor Rick Liu’s Usher RNA editing research. This support comes at a pivotal moment, as I prepare to return to Australia from the US and establish my new lab. I’ll be able to hit the ground running and continue pushing forward research that we hope will change lives.”