AAV Mediated Rescue of Neuronal Ceroid Lipofuscinosis-Like Retinal Disease

Seminar | February 10 | 11:10 a.m.-12:30 p.m. | 489 Minor Hall

 Emilia Zin, John Flannery Lab

 Neuroscience Institute, Helen Wills

Mutations to the progranulin gene (GRN) can cause neuronal ceroid lipofuscinosis (NCL), known as CLN11. The deficiency of the protein progranulin leads to neuronal death both in the brain and retina, in part due to endolysosomal dysfunction. Therefore, restoring or enhancing progranulin via a gene therapy based approach represents an attractive target for treating CLN11. An adeno-associated virus (AAV) capsid that can infect all layers of the retina (7m8) can target all retinal neurons with a healthy copy of the GRN gene in a GRN-/- mouse line. This approach allows us to determine the time dependency and potential effectiveness of such gene delivery by optical coherence tomography (OCT), histology and RT-qPCR analysis of the retina.