A breakthrough study from Japanese scientists offers promising genome editing solutions for hereditary hearing loss caused by the GJB2 R75W mutation.
Scientists from Juntendo University and The University of Tokyo have made a significant advancement in the treatment of genetic hearing loss linked to the GJB2 R75W mutation. Their study, published in JCI Insight, showcases a groundbreaking adeno-associated virus (AAV)-based genome editing approach, which holds promise for those affected by this form of hereditary hearing loss.
The GJB2 gene mutation is known to disrupt auditory function due to its impact on the integrity of gap junction plaques, which are crucial for cell communication in the inner ear. While recessive mutations can typically be treated through gene replacement therapies, dominant-negative mutations like R75W necessitate a more nuanced approach such as genome editing to restore the function of the wild-type protein.
The research team, which includes Associate Professor Dr Kazusaku Kamiya, Assistant Professor Dr Takao Ukaji, and Dr Osamu Nureki, has developed a specialised miniature base editing tool named SaCas9-NNG-ABE8e, designed to work efficiently with AAV vectors. This tool was incorporated into an AAV vector engineered to specifically target the inner ear cells affected by the mutation.
In their experiments, the researchers evaluated the AAV-based therapy on human cells harbouring the GJB2 R75W mutation. The results demonstrated successful genome editing, with the restoration of gap junction plaques and improved cell-to-cell communication. These promising outcomes were subsequently corroborated in transgenic mouse models, which exhibited the formation of junction plaques comparable to those found in normal, or wild-type, cells.
Dr Kamiya remarked, “The overwhelming majority of mutations causing hereditary hearing loss involve the GJB2 gene. Our research can contribute to the development of gene therapy to tackle the increasing incidence of hereditary hearing loss patients.” This underscores the broader impact that such research could have on addressing the growing prevalence of genetic hearing loss in patients.
The findings indicate that AAV genome editing not only holds potential for enhancing therapeutic results but may also reduce associated costs. Additionally, the research team envisions the possibility of adapting this innovative therapy for other genetic mutations linked to hearing loss, paving the way for substantial advancements in the treatment of genetic deafness.
Source: Noah Wire Services
