Gene Therapy of Severe Inherited Photoreceptor Diseases due to Mutations in Large Genes

Inherited retinal diseases (IRD) are a major cause of worldwide, untreated blindness. The majority of cases are due to mutations in genes expressed in retinal photoreceptor cells (PR).
Recently, our lab group has contributed to the finding that gene therapy using adeno-associated viral vectors (AAV) is safe and effective in patients with rare forms of inherited childhood blindness, and this bodes well for treatment of the more common photoreceptor-specific IRD. Several genes expressed in PR and involved in IRD are larger in size than what is tolerated by AAV vectors. While other gene therapy vectors derived from either adenovirus (Ad) or lentiviruses (LV) have larger cargo capacities than AAV, they do not effectively infect have PR.
Our goal is to overcome the challenge of transferring large genes to PR in order to develop therapies for common IRD. We are using a system to increase AAV cargo capacity based on dual AAV vectors, each containing one of the two halves of a large gene reconstituted upon co-infection of target cells and intermolecular AAV joining. The results from this project may provide novel treatment options for common severe blinding conditions.

The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.