New gene editing approach shows promise for specific Usher Syndrome a rare cause of hearing and vision loss
Scientists and clinicians from the Center of Ophthalmology in Tübingen together with colleagues from the Department of Oncology tried a EDCas9, which emerges as a flexible and powerful editing approach for addressing the pathogenic USH2A:7595-2144A>G variant
Many inherited genetic diseases are caused by errors in how cells read and process genetic information — a problem known as "missplicing." One way to fix this is with special molecules called antisense oligonucleotides, but these offer only a temporary solution. Another option, CRISPR/Cas9 gene editing, often removes larger sections of DNA to correct these errors, which can increase the risk of unintended damage to the genome.
In this study, the scientists explored a safer and more targeted CRISPR approach to treat a specific genetic change (called USH2A:c.7595-2144A>G) that leads to Usher Syndrome — a condition that causes hearing and vision loss. Instead of using two cutting tools (gRNAs) to remove a large section, they tested using only one, combined with either the standard Cas9 protein or a modified version called EDCas9 (Cas9 fused to another protein named TREX2).
They found that EDCas9 more reliably removed the faulty part of the gene that causes missplicing. It worked well in both lab-made genetic models and in cells from a person with Usher Syndrome. EDCas9 also showed a safer editing pattern and avoided unwanted changes elsewhere in the DNA. Additionally, they successfully delivered EDCas9 into cells using virus-like particles, which can offer a temporary and controlled way to apply the treatment.
In summary, their results show that EDCas9 is a promising and precise gene-editing tool to fix the specific genetic error that causes this form of Usher Syndrome. It may lead to safer and more effective future therapies.
Here is the link to the original Aricle: Single gRNA Cas9 and Enhanced-Deletion Cas9 rescue a recurrent USH2A-related splicing defect
By Pietro De Angeli, Salome Spaag, Stefanida Shliaga, Arturo Flores Tufiño, Malte Ritter, Masoud Nasri, Katarina Stingl, Laura Kühlewein, Bernd Wissinger, Susanne Kohl
