Viral Vectors
Inherited retinal dystrophies (IRDs) are a group of diseases that are due to mutations in specific genes that are important for the structure or function of the retina. They are characterized by progressive vision loss due to degeneration of the light-sensing photoreceptors. There are over 270 IRDs, each due to a mutation in a specific gene. Over recent years there has been much progress in terms of gene supplementation therapy for IRDs, whereby a normal copy of the diseased gene is introduced into the retina to compensate for the defective copy. To introduce a gene into retinal cells, a vehicle is needed. The most currently used vehicle is a vector derived from an adeno-associated virus (AAV). AAV vectors are safe and effective, but their limitation lies in the size of the cargo they can carry (<4.7 kb). Moreover, the two genes that are most commonly responsible for IRDs, USH2A and EYS, both exceed 4.7 kb. Here, we aim to test the ability of a novel viral vector with a much larger cloning capacity to enter the human retina. For these proof-of-concept studies we will use retinal organoids, 3D structures that reproduce the photoreceptor layer of the retina, differentiated from induced pluripotent stem cells (iPSC) of patients. In this way, we will test the ability of this new vector platform to overcome the natural barriers present in the retina to reach the photoreceptors and restore a normal morphology to the diseased cells.
