Researchers have developed a gene editing therapy that could potentially treat Stargardt disease, the most common form of inherited macular degeneration.  

The study, published in Nature Medicine, demonstrates the therapeutic use of a precision gene editing technology called base editing. 

The research team, led by Bence György and Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel (IOB), in collaboration with scientists from Beam Therapeutics led by David Bryson and Giuseppe Ciaramella, developed a highly optimised adenine base editor delivered by adeno-associated viral vectors (AAVs) to correct the most common mutation associated with Stargardt disease. 

“Our approach achieved remarkably high levels of gene correction,” said Dr György. “We observed average editing rates of 75% in cone cells and 87% in retinal pigment epithelial cells. These results far exceed what we believe is necessary to provide clinical benefit to patients.” 

Importantly, the team demonstrated the effectiveness of their technique in multiple models, including human tissues: human retinal organoids, stem cell-derived retinal pigment epithelial cells, human retinas, and human retinal pigment epithelial cells. 

Alissa Muller, the study’s first author, emphasised the precision and safety of their technique: “We conducted extensive off-target analysis and found no evidence of unintended editing in the retina or other parts of the body. This is crucial for the development of a safe and effective therapy.” 

The researchers also noted that their base editing approach could potentially be adapted to treat other inherited retinal diseases caused by similar types of mutations.  

“This work exemplifies a key goal of IOB: combining our deep understanding of retinal biology and vision with breakthrough technologies to develop novel therapies for vision loss,” added Dr Roska.

Diana Spencer, Senior Digital Content Editor, DDW