scAAV-ie-CAG-GFP

Hearing loss is one of the most common sensory disorders, affecting more than 6.8% of the world's population (about 500 million people). Currently, hearing loss is treated with hearing aids, which can amplify sound, enhance sound transmission, or directly stimulate neurons. This approach is currently the best choice for treating hearing loss, but unfortunately, it still has limitations in auditory sensitivity and the perception of natural sounds in noisy environments. In recent years, gene therapy has become a potential and promising strategy for treating genetic diseases. The first adeno-associated virus (AAV)-mediated gene therapy for patients with rare genetic eye diseases was approved by the US Food and Drug Administration (FDA) in 2017, which brought hope for gene therapy for hearing loss. AAV has shown clinical efficacy and safety in multiple organs, including the liver and retina. Some studies have tested AAV-mediated cochlear gene therapy in animal models and achieved promising results. Researchers designed an AAV variant, AAV-ie (AAV-inner ear), for mouse cochlear gene delivery. In vitro transduction of mouse organotypic explants showed that AAV-ie could infect nearly 90% of supporting cells (SCs). In vivo experiments showed that after these AAVs were injected into the cochlea through the round window membrane (RWM), the efficiency of AAV-ie transduction of SCs was significantly higher than that of other AAV serotypes. RWM injection of AAV-ie was safe, and HCs and hearing function were well preserved. In addition, after Atoh1 gene delivery into the mouse cochlea via AAV-ie, many new hair cells (HCs) were generated, indicating that AAV-ie vectors have the potential for HC regeneration.