AAV Gene Therapy in Inherited Retinal Diseases (IRDs)

IRDs occur when faults in specific genes prevent the retina from functioning properly, leading to progressive vision loss. A key challenge is that most IRDs affected cells do not naturally repair themselves, meaning that once retinal cells are lost, they cannot be replaced. Gene therapy aims to intervene before this happens by delivering functioning copies of the faulty gene directly to the cells of the retina.

One of the most common delivery tools in gene therapy is the adeno-associated virus (AAV). AAV is a, nonreplicating virus that can carry genetic instructions into retinal cells. It has become a preferred vector because of its excellent safety record, ability to target specific retinal layers, and long-lasting expression once delivered. AAV gene therapies are typically administered through a precise surgical procedure in which a small amount of vector is injected under the retina. This approach allows treatment to reach the photoreceptors or retinal pigment epithelium (RPE), the cells most often affected in IRDs.

AAV gene therapy is particularly well suited to diseases caused by small or medium sized genes, as these fit within the AAV’s carrying capacity. However, faults in genes like ABCA4, which cause Stargardt disease or MYO7A, which causes Usher Syndrome Type1B, are too large to fit into a single AAV vector. AAVantgarde is exploring alternative approaches, such as dual AAV delivery platforms, where the gene is split into two parts and reassembled inside the cell after being injected into the back of the eye.

Because IRDs often progress slowly, clinical trials with an AAV gene therapy require sensitive imaging and functional tests to detect potential improvements over time.

Overall, the field of retinal gene therapy is advancing rapidly. A growing number of clinical trials are underway, and companies like AAVantgarde are continually improving AAV delivery methods. As understanding deepens and technology evolves, AAV gene therapy is expected to become a key pillar in the treatment landscape for inherited retinal diseases, offering hope to patients and families affected by conditions that were previously untreatable.