Breakthrough gene editing technique offers hope for Stargardt disease patients
Researchers have developed a highly efficient gene editing therapy that could potentially treat Stargardt disease, the most common form of inherited macular degeneration. This groundbreaking study, published in Nature Medicine on 8 January 2025, demonstrates the therapeutic use of a precision gene editing technology called base editing.
Stargardt disease affects 1 in 6,500 individuals and often results in legal blindness. There is currently no effective treatment available. 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 optimized 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. 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.
BENCE GYÖRGY
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. This comprehensive approach provides very strong evidence for the potential translatability of the treatment to human patients.
We are very encouraged to observe this level of potency in these relevant models at clinically relevant doses.
DAVID BRYSON
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.
ALISSA MULLER
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. These results represent a significant advancement in the field of ocular gene therapy. The next steps may include further safety studies and preparations for clinical trials. If successful, this gene editing approach could offer hope to thousands of individuals affected by Stargardt disease and potentially other inherited retinal disorders.
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.
BOTOND ROSKA
Original Publication
High-efficiency base editing in the retina in primates and human tissues
Alissa Muller, Jack Sullivan, Wibke Schwarzer, Mantian Wang, Cindy Park-Windhol, Pascal W. Hasler, Lucas Janeschitz-Kriegl, Mert Duman, Beryll Klingler, Jane Matsell, Simon Manuel Hostettler, Patricia Galliker, Yanyan Hou, Pierre Balmer, Tamás Virág, Luis Alberto Barrera, Lauren Young, Quan Xu, Dániel Péter Magda, Ferenc Kilin, Arogya Khadka, Pierre-Henri Moreau, Lyne Fellmann, Thierry Azoulay, Mathieu Quinodoz, Duygu Karademir, Juna Leppert, Alex Fratzl, Georg Kosche, Ruchi Sharma, Jair Montford, Marco Cattaneo, Mikaël Croyal, Therese Cronin, Simone Picelli, Alice Grison, Cameron S. Cowan, Ákos Kusnyerik, Philipp Anders, Magdalena Renner, Zoltán Zsolt Nagy, Arnold Szabó, Kapil Bharti, Carlo Rivolta, Hendrik P. N. Scholl, David Bryson, Giuseppe Ciaramella, Botond Roska and Bence György
Nat Med. 2025 Feb;31(2):490-501.
doi: 10.1038/s41591-024-03422-8. Epub 2025 Jan 8.
