In recent years, breakthroughs in genetic research have opened the door to treating inherited retinal diseases (IRDs), such as retinitis pigmentosa, Usher syndrome and Stargardt’s disease.

Only a few years ago, being diagnosed with one of these IRDs meant a gradual loss of vision was all but a certainty, but treatments for these diseases are now on the horizon.

One gene therapy is now available for a rare form of retinitis pigmentosa, and treatments are being developed for a range of other conditions.

Collectively, IRDs are the most common cause of blindness in working-age Australians. But despite sharing a name, the genetic mistakes that cause each IRD are different. A treatment that works for one of the 250 genes known to cause IRDs will not work for another.

Satheesh Kumar is a graduate researcher in CERA’s Genetic Engineering Research Unit. He is working with Associate Professor Guei-Sheung (Rick) Liu to develop new ways of treating disease that would mean more treatments for different IRDs.

Editing vs replacing

A person’s DNA includes all the instructions that cells need to operate – and mistakes in this sequence are what cause a person’s body to not operate properly.

In the case of IRDs, this means vision loss.

“Before starting my PhD, I was an honors student in Queensland and became interested in gene editing, because there are now a lot of new technologies that are trying to treat genetic diseases,” Kumar says.

These tools are safe viruses which carry a correct version of the gene, but they aren’t suitable for every type of disease.

“In traditional gene therapy, a new gene is introduced without fixing the root cause,” Kumar says.

“The mutated gene is still in the cell, which can sometimes be harmful. And for a lot of IRDs, the tools we have just aren’t suitable.”

The Genetic Engineering team is using a technology called RNA base editing to try and correct these mistakes instead.

While DNA is the instruction booklet for cells to function, it is RNA that carries out these instructions by transmitting their message to build the different parts of our cells.

“Gene editing that targets RNA enables us to directly correct the mistake causing the disease,” Kumar says.

“We aim to correct the genetic errors responsible for these diseases at the molecular level, which could lead to new treatments in the future.”

To the clinic

Kumar is hopeful that IRDs once believed to be untreatable will eventually have therapies, thanks to improved understanding of the genetic causes and better tools to produce working genes.

“At CERA, when we do research, we are always asking ‘how do we turn this into a tool for the clinic?’

“When I’m working with Associate Professor Liu, we want to dive deeper into our understanding of these tools – and alongside many other people around the world we are constantly learning new things about them.

“Learning more about the basic mechanisms of these tools means we can improve them, so they can be useful for even more diseases.”

The team’s work requires significant collaborations with others.

“Associate Professor Liu and I work with a lot of collaborators to make sure these tools are clinically relevant – especially as some of these tools might also be helpful not just for vison loss but also for hearing loss,” he says.

“I’m excited about the new treatments for many conditions that our research is working towards.”

Associate Professor Liu’s RNA editing research is supported by an NHMRC Ideas Grant.