AAV-based gene therapies for inherited retinal disorders due to mutations in large genes

Adeno-associated viral (AAV) vectors are widely used for in vivo gene therapy; however, their limited packaging capacity poses a major challenge for treating inherited retinal disorders caused by large genes. 

To address this, we have developed different strategies based on dual AAV platforms and AAV-mediated genome editing approaches. In the dual AAV strategy, large therapeutic proteins are split into smaller fragments, delivered via separate vectors, and reconstituted in target cells. In parallel, we are developing genome editing approaches to enable the integration of large DNA templates into diseased genes, allowing correction of multiple mutations with a single therapeutic construct. 

These methodologies aim to overcome current delivery constraints and enable broader, mutation-independent therapeutic applications. In this seminar, I will present the conceptual framework of these approaches, summarize preclinical data obtained in relevant models of inherited retinal diseases, and discuss their potential to expand the therapeutic landscape.