This study aimed to use a new genetic technology called “RNA gene editing” to correct genetic mutations that cause inherited retinal diseases, which are a leading cause of blindness in working-age adults in Australia. The goal was to also develop a more effective and generalisable treatment approach, which could have a significant impact on the management of inherited retinal diseases and other genetic diseases.
Project Results and Impact
In this project, the research team designed and compared two newly developed RNA base editors (CRISPR-dCas13 and CRISPR-inspired RNA targeting system) on the editing of the RPE65 gene, the common single-base mutation found in Leber Congenital Amaurosis. By using retinal pigment epithelium cells which are the cells that support and nourish the light sensitive cells in the retina, their results showed that the CRISPR-dCas13 RNA base editor could effectively correct the single-base mutation on the RPE65 gene and restore the protein expression terminated by the mutation.
The team are now expanding this study to investigate the feasibility of using this RNA base editor to correct mutations in other inherited retinal diseases, such as Usher Syndrome type 2A, Usher Syndrome type IF, and X-linked Retinoschisis. Moreover, they are also ongoing to validate the efficacy of RNA base editing in clinically relevant animal models to demonstrate the efficacy or preservation of the retinal function from mutation-caused retinal degeneration. The outcome of their study would be a significant step toward a viable treatment for inherited retinal degeneration.
Published peer reviewed journal articles
Kumar S and Liu GS. Recent advances in RNA-targeting therapy for neurological
diseases (2023). Neural Regeneration Research, accepted on 21/12/2022.
This project was recently featured in a Retina Australia webinar. You can view a recording of this event here.
A summary of the webinar presentation can be viewed here.
Associate Professor Guei-Sheung (Rick) Liu
Centre for Eye Research Australia, Melbourne
Professsor Bang Bui, University of Melbourne
Dr Thomas Edward, Centre for Eye Research Australia, Melbourne